WO2019190402A1

WO2019190402A1 - Biocompatible ophthalmic device

Info

Publication number: WO2019190402A1
Application number: PCT/SG2019/050174
Authority: WO
Inventors: Lakshminarayanan RAJAMANI; Chetna DHAND; Roger Beuerman
Original assignee: Singapore Health Services Pte Ltd
Priority date: 2018-03-28
Filing date: 2019-03-28
Publication date: 2019-10-03

Abstract

Disclosed is a biocompatible ophthalmic device comprising: a core material; a first component which is coating the surface of the core material; and a second component which is linked to the first component by a bond; wherein the first component comprises cross-links of at least one catecholamine compound and the second component comprises at least one antimicrobial peptide and/or at least one antimicrobial polymer. Also disclosed are methods of preventing, suppressing and/or treating an ophthalmic infection in an eye of a subject, devices for use in preventing, suppressing and/or treating an ophthalmic infection, methods of manufacturing biocompatible ophthalmic devices, and a kit for preparing the ophthalmic device. Preferably the ophthalmic device is a contact lens and the catecholamine compound is dopamine.

Description

BIOCOMPATIBLE OPHTHALMIC DEVICE

FIELD OF THE INVENTION

[0001] The present invention generally relates to devices for the eyes. In particular, the present invention relates to antimicrobial-coated devices for the eyes and methods of manufacturing said devices.

BACKGROUND OF THE INVENTION

[0002] Ophthalmic infections, if left untreated, can cause severe damage to the eyes of sufferers, leading to vision loss and blindness. Microbial keratitis (MK) i.e., infection of the cornea, is the fourth leading cause of ocular morbidity and blindness worldwide after cataract, glaucoma and age-related macular degeneration. MK affects an estimated 500,000 patients annually, and is known to cause corneal ulcer, which is often associated with contact lens wear. Extended wear contact lenses is one of the major risk factors for the development of MK in the developed countries. While contact lenses offer easy and innovative solution for vision correction, their non-compliant usage may lead to severe ocular complications. In a recent single centered study, about 44% of MK was found to be associated with contact lens wear. About 56-65% of contact lenses harbor microorganisms, including pathogenic bacteria when removed from the eye. While MK remains a major contact lens-associated complication, soft contact lens wear is associated with a significant number of these cases. The adherent microorganisms, including pathogenic bacteria, form biofilms on contact lenses and invade and colonize the cornea.

[0003] Considering that MK is a growing global health issue, attempts are in progress to develop antimicrobial contact lenses either i) by impregnating antimicrobial agents within the bulk of the lenses or ii) by functionalizing the contact lens surface with antimicrobial components. Both covalent and non-covalent functionalization of contact lenses have been attempted to prevent microbial colonization and biofilm formation in order to avert the adverse effects associated with microbials. The methods incorporate active antimicrobial ingredients e.g., silver, furanones, polyquatemium compounds, non-steroidal anti inflammatory drugs, selenium, cationic antimicrobial peptides or anti-adhesive or passive components such as phosphotidyl choline or polyethyleneoxide dialdehyde. In the non- covalent approach, microbial adhesion on commercial contact lenses soaked in furanonone or colloidal silver nanoparticles have been studied. Furanone impregnated lenses did not show adequate efficacy in preventing bacterial adhesion. Further, toxicity and coloration of the tissues associated with silver was a major concerns, despite its efficacy in decreasing bacterial adhesion. Several studies have demonstrated in vitro antimicrobial efficacy and in vivo safety of organo selenium compounds and antimicrobial peptides that were covalently attached to silicone hydrogel contact lenses. The later studies demonstrated that peptides covalently attached to contact lenses inhibited the adhesion of bacteria and fungi in vitro as well as reduced contact lens-induced acute red eye and contact lens-induced peripheral ulcers.

[0004] However, covalent attachment of antimicrobial peptidic compounds to the surface of the contact lens requires non-trivial modification of the contact lens surface and the antimicrobial peptides or compounds. In view of the above, there is a need to provide alternative biocompatible ophthalmic devices and alternative methods to manufacture said devices.

SUMMARY

[0005] In one aspect, the present disclosure provides a biocompatible ophthalmic device comprising: a core material; a first component which is coating the surface of the core material; and a second component which is linked to the first component by a bond; wherein the first component comprises cross-links of at least one catecholamine compound and the second component comprises at least one antimicrobial peptide and/or at least one antimicrobial polymer. In one example, the bond is a covalent bond or non-covalent bond.

[0006] In one example, the catecholamine compound is selected from the group consisting of (S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid (or L-3,4-dihydroxyphenylalanine or Levodopa); (R)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid; (or D-3,4- dihydroxyphenylalanine or Dextrodopa); L-3,4-dihydroxyphenylalanine methyl ester; D-3,4- dihydroxyphenylalanine methyl ester; 4-(2-aminoethyl)benzene-l,2-diol (or 3,4- dihydroxyphenethylamine or Dopamine); 4-[(lR)-2-amino-l-hydroxyethyl]benzene-l,2-diol (or Norepinephrine or Noradrenaline); 4-[(lS)-2-amino-l-hydroxyethyl]benzene-l,2-diol;

(R)-4-(l-Hydroxy-2-(methylamino)ethyl)benzene-l,2-diol (or Epinephrine or Adrenaline);

(S)-4-(l-Hydroxy-2-(methylamino)ethyl)benzene-l,2-diol; Adrenalone; Carbidopa; Colterol; DimethylDOPA; Dioxifedrine; Dioxethedrin; 5-hydroxydopamine; Dobutamine; Dopexamine; Droxidopa; a-methylnorepinephrine (or Corbadrine or Nordefrin); Ethylnorepinephrine; Etilevodopa; Isoetharine; Hexoprenaline; N-methyladrenalone; Norbudrine; and Oxidopamine. In one example, the catecholamine compound is dopamine (or 4-(2-aminoethyl)benzene-l,2-diol or 3,4-dihydroxyphenethylamine or

norepinephrine (4-[(lR)-2-amino-l-hydroxyethyl]benzene-

l,2-diol; Noradrenaline;

[0007] In one example, the ophthalmic device is selected from the group consisting of optical prosthetic device, intraocular lens, artificial eye, contact lens, bandage contact lens, device care box, and ophthalmic surgical device. In one example, the ophthalmic device is selected from the group consisting of a contact lens, a bandage contact lens, and an intraocular lens. In one example, the contact lens or the bandage contact lens or the intraocular lens has a diopter value within the range of -0.5 to +0.5 diopters from the diopter value of the core material. In one example, the contact lens or the bandage contact lens or the intraocular lens has a diopter value within the range of -0.2 to +0.2 diopters from the diopter value of the core material.

[0008] In one example, the core material is selected from the group consisting of hydrogel, poly(HEMA) hydrogels, silicone hydrogel, metals, sapphire (Al₂0₃), quartz, stainless steel, NiTi, Silicon, polymer, Acrylate/Methacylate Copolymer, glass, and silicon nitride. In one example, the core material is a hydrogel. In one example, the hydrogel is selected from the group consisting bufilcon A, epsifilcon A, etafilcon A, focofilcon A, methafilcon A, methafilcon B, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ocufilcon F, perfilcon A, phemfilcon A, tetrafilcon B, and vifilcon A. In one example, the hydrogel is etafilcon A.

[0009] In one example, the antimicrobial peptide is selected from the group consisting of a peptide comprising at least one lysine residue (amino group), a peptide comprising at least one cysteine residue (thiol group), or a peptide comprising at least one histidine residue (imidazole group). In one example, the antimicrobial peptide comprising at least one lysine residue is selected from the group consisting of RGRKVVRRKK (SEQ ID NO.: 1) (monomer), RGRKVVRRKKRRVVKRGR (SEQ ID NO.: 2) (linear retrodimer),

(RGRKVVRR)₂KKKi (bAMP B2088), [(RGRKVVRR)₂K]₂KKi (bAMP B4010), [( AGRKVVRR)₂K] ₂KK_I, [(RARKVVRR)₂K]₂KKi, [(RGAKVVRR)₂K] ₂KKi, [(RGRA VVRR)₂K] ₂KK_I, [(RGRKAVRR)₂K]₂KKi, [(RGRKVARR)₂K]₂KKi, [(RGRKVV AR)₂K] ₂KK_I, [(RGRKVVRA)₂K]₂KKi; [(RGAA VVRR)₂K] ₂KK_I, [(RGRKVVAA)₂K]₂KKi, [(RGAKAVRR)₂K]₂KK_I, [(RGRKAARR)₂K] ₂KK_I, [(RGAAAVRR)₂K]₂KK_I, [(RGAKAARR)₂K]₂KK_I, [(RGRAAARR)₂K] ₂KK_I,

[(RGAAAARR)₂K]₂KK_I, [(RGRKAAAA)₂K]₂KK_I; [(GRKVVRR)₂K] ₂KK_I,

[(RKVVRR)₂K]₂KK₁, [(KVVRR)₂K]₂KK₁, [(VVRR)₂K]₂KK₁, [(VRR)₂K]₂KK₁,

[(RR)₂K]₂KK_I, [(R)₂K]₂KK_I; [(VRGRVRKR)₂K] ₂KK_I (scrambled pAMP B4010 DK), wherein i = 0 or 1. In one example, the antimicrobial peptide comprising at least one lysine residue is [(RGRKVVRR)₂K]₂KK (SEQ ID NO.: 56) (or

or bAMP B4010).

[0010] In one example, the antimicrobial polymer is a polymer comprising at least one amino group, a polymer comprising at least one thiol group, a polymer comprising at least one imidazole group. In one example, the antimicrobial polymer comprising at least one amino group is selected from the group consisting of Poly-L-Lysine, Poly-D-Lysine, e-poly- L- Lysine, linear Polyethylenimine (linear PEI), and branched Polyethylenimine (branched PEI).

[0011] In one example, the first component and the second component reduces the viability of a bacterium or a fungus. In one example, the first component and the second component prevents the adhesion of a bacterium or a fungus to said device.

[0012] In one example, the bacterium is selected from the group consisting of Pseudomonas spp., Staphylococcus spp., and Serratia spp.. In one example, the bacterium is selected from the group consisting of MRSA (Methicillin-resistant Staphylococcus aureus), Staphylococcus aureus, and Pseudomonas aeruginosa.

[0013] In one example, the fungus is selected from the group consisting of Fusarium spp..

[0014] In another aspect, the present disclosure provides a method of preventing, r suppressing and/or treating an ophthalmic infection in an eye of a subject comprising the placement of a device as disclosed herein in the eye of the subject. In yet another aspect, the present disclosure provides a device as disclosed herein for use in preventing, suppressing and/or treating an ophthalmic infection in a subject. In one example, the ophthalmic infection is selected from the group consisting of blepharitis, microbial keratitis, dacryocystitis, and orbital cellulitis. In one example, the ophthalmic infection is microbial keratitis.

[0015] In yet another aspect, the present disclosure provides a method of manufacturing a biocompatible ophthalmic device disclosed herein, wherein the method comprises contacting a core material with a mixture comprising at least one catecholamine compound, at least one antimicrobial peptide and/or at least one antimicrobial polymer, and a biocompatible buffer to allow the formation of a coat on the surface of the core material; and removing excess first component, second component, and biocompatible buffer. In one example, the biocompatible buffer is an inorganic buffer. In one example, the inorganic buffer is selected from the group consisting of, phosphate buffer, carbonate buffer or sodium bicarbonate (NaHC0₃) buffer, and ammonium bicarbonate buffer (or (NH₄)HC0₃). In one example, the inorganic buffer is carbonate buffer (or sodium bicarbonate or NaHC0₃ buffer). In one example, the concentration of the catecholamine compound in the mixture is from 0.1 mg/mL to 0.5 mg/mL. In one example, the concentration of the catecholamine compound in the mixture is 0.25 mg/mL. In one example, ratio of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture is from 1:1 to 1:10. In one example, the ratio of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture is 1:2 or 1:8.

[0016] In another aspect, there is provided a kit for preparing a biocompatible ophthalmic device as disclosed herein, the kit comprising: a core material; and a mixture comprising: a first component comprising at least one catecholamine compound; a second compound comprising at least one antimicrobial peptide and/or at least one antimicrobial polymer; and a biocompatible buffer. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The disclosure will be better understood with reference to the detailed description when considered in conjunction with the non-limiting examples and the accompanying drawings, in which:

[0018] Fig. 1 shows a set of photographs comparing the transparency of several contact lenses that are prepared under various conditions. Fig. 1A depicts an uncoated contact lens (UCL), Fig. IB depicts a polydopamine-coated contact lens (pDA-CL), Fig. 1C depicts an antimicrobial peptide and polydopamine-coated contact lens (bAMP-pDA-CL), and Fig. ID depicts a yMangostin and polydopamine-coated contact lens (yMG-pDA-CL). Thus, Fig. 1 show that both bAMP-pDA-CL and yMG-pDA-CL displayed no loss of optical transparency when compared to UCL and that the coatings had minimal impact on the CL optical properties as well as functional properties.

[0019] Fig. 2 depicts a set of spectra obtained by X-ray Photoelectron Spectroscopy (XPS) analysis of contact lenses. Fig. 2A, 2B, and 2C respectively depict core level (A) Cls, (B) Nls, and (C) Ols spectra of UCL, pDA-CL, bAMP-pDA-CL and yMG-pDA-CL. Fig. 2D, 2E, 2F, and 2G respectively depict deconvoluted Cls spectra of (D) UCL, (E) pDA-CL, (F) bAMP-pDA-CL, and (G) yMG-pDA-CL. Fig. 2H, 21, and 2J respectively depict deconvoluted Nls spectra of (H) pDA-CL, (I) bAMP-pDA-CL, and (J) yMG-pDA-CL. The points in Fig. 2A to 2C and Fig. 2E to 2J correspond to the experimental raw data and the bell shape curves in Fig. 2A to 2C and Fig. 2E to 2J correspond to the bonding environments around C and N, respectively, after deconvolution of the raw data (indicated by the vertical lines). Fig. 2K is a graph showing the relative increase in nitrogen in the coated lenses with respect to the uncoated contact lens. Thus, Fig. 2 shows that changes in the shape and peak positions of the coated contact lenses (e.g. pDA-CL, bAMP-pDA-CL, and yMG- pDA-CL) when compared to the uncoated contact lens (UCL) indicate the presence of pDA coating over the contact lenses.

[0020] Fig. 3 depicts a set of images obtained by Atomic Force Microscopy (AFM) that shows the change in surface topography and root mean square surface roughness (R_q) of the contact lens with different coating materials. Fig. 3A, 3B, 3C, and 3D respectively correspond to Atomic Force Microscopy (AFM) images of the surface of (A) UCL, (B) pDA- CL, (C) bAMP-pDA-CL, and (D) yMG-pDA-CL. Thus, Fig. 3 shows that attachment of antimicrobials such as antimicrobial peptide (bAMP) or yMangostin (yMG)) to the surface of the contact lenses result in moderate increase in their surface roughness. Moderate increase in surface roughness may not affect the comfort of wearing the contact lenses.

[0021] Fig. 4 depicts a set of graphs showing the effects of the antimicrobials such as the antimicrobial peptide (bAMP) or yMangostin (yMG)) on the coated contact lenses against various bacteria. Fig. 4A and 4B respectively show bar graphs depicting the viable counts of various (A) gram-positive and (B) gram-negative bacteria after incubating with uncoated contact lens (UCL), bAMPs-pDA-CL and yMG-pDA-CL for 24 hours at 37 °C. *p<0.05, **r<0.01, ***p<0.00l and ****p<0.000l compared to control inoculum by t-test or l-way ANOVA. Fig. 4C and 4D respectively show line graphs depicting the antimicrobial activity assessment of the contact lenses against (C) MRS A DM21455 and (D) P. aeruginosa DM23155 after soaking in lens-care solution over a period of 2 weeks. Thus, Fig. 4 shows decrease in bacterial viability and that the coated contact lenses could prevent bacterial colonization for up to 14 days.

[0022] Fig. 5 depicts a set of images obtained using confocal microscopy. Fig. 5A and 5B respectively show results of Live/Dead microbial cell staining on uncoated and various coated contact lenses after (A) 1 day and (B) 3 day post-incubation with P. aeruginosa, S. aureus and MRSA. Contact lenses were incubated with 3 x 10 CFU/mL of the microbes and were monitored for microbial adhesion. Fig. 5 shows that fewer individual colonies of S. aureus and MRSA were visible on the surface of both bAMP-pDA-CL and yMG-pDA-CL coated CLs at day 1 and 3. This result indicates that S. aureus and MRSA biofilm formation is inhibited by the contact lenses coated with bAMP-pDA-CL and yMG-pDA-CL.

[0023] Fig. 6 depicts a set of micrographs obtained using scanning electron microscopy (SEM). The SEM micrographs of Fig. 6 show the surfaces of uncoated and various coated contact lenses (coated with pDA, bAMP-pDA and yMG-pDA) after a 1 day incubation with

P. aeruginosa, MRSA and S. aureus. Contact lenses were incubated with 3 x 10 CFU/mL of the various microbes and were monitored for microbial adhesion. The microbes that adhered to the surface of antimicrobial-coated contact lenses (bAMP-pDA-CL and yMG-pDA-CL) displayed considerable shrinkage and loss of membrane integrity, indicating that the antimicrobials on the coated contact lenses have bactericidal activity.

[0024] Fig. 7 depicts a set of micrographs obtained using scanning electron microscopy (SEM). The SEM micrographs of Fig. 7 show the surfaces of uncoated and various coated contact lenses (coated with pDA, bAMP-pDA and yMG-pDA) after 6 day incubation with P. aeruginosa, MRSA and S. aureus.. Contact lenses were incubated with 3 x 10 CFU/mL of the various microbes and were monitored for microbial adhesion. The microbes that adhered to the surface of antimicrobial-coated contact lenses (e.g. bAMP-pDA-CL and yMG-pDA- CL) displayed considerable shrinkage and loss of membrane integrity, indicating that the bactericidal activity of the antimicrobials on the coated contact lenses is maintained for at least 6 days.

[0025] Fig. 8 depicts a set of images obtained using confocal microscopy and a bar graph showing the cytocompatibility of the coated contact lenses. Fig. 8A, 8B, 8C, 8D, and 8E respectively shows telomerase-immortalized human corneal epithelial (hTCEpi) cells and human primary corneal stromal fibroblasts (hCSFb) grown on (A) tissue culture plate (negative control), (B) with pDA-CL, (C) with bAMP-pDA-CL, (D) with yMG-pDA-CL, and (E) with Triton X (positive control). Scale bar measures 100 pm and 25 pm for hTCEpi and hCSFb cells, respectively. Fig. 8F shows the results of lactase dehydrogenase (LDH) membrane integrity assay that reveal the % cell viability of hTCEpi and hCSFb cells for various coated contact lenses. Thus, Fig. 8 shows that normal cellular morphology of hTCEpi and hCSFb cells on the surface of pDA-CL and bAMP-pDA-CL indicate that the antimicrobial peptide coated contact lens is biocompatible.

[0026] Fig. 9 shows a graphical illustration depicting the methodology adopted to design antimicrobial contact lenses and the covalent and non-covalent interactions involved in the fabrication of B40l0-pDA-CL and yMG-pDA-CL, respectively.

[0027] Fig. 10 shows a graphical illustration depicting an exemplary method for the manufacture of the biocompatible ophthalmic device.

[0028] Fig. 11 shows a photograph depicting contact lens coated under non-optimal conditions and thus the coated contact lens shows discolouration, precipitates, and poor clarity.

[0029] Fig. 12 shows photographs of the contact lenses prepared at various dopamine PL ratios. Fig. 12A, 12B, 12C, 12D and 12E respectively refer to (A) CL0 (uncoated CL), (B) CL1 (dopamine :ePL = 0.T0.1), (C) CL2 (dopamine:ePL = 0.25:0.25), (D) CL3 (dopamine PL = 0.25: 1.0), (E) CL4 (dopamine PL = 0.25:2.0) Fig. 12F shows the optical transmission spectra of the prepared contact lenses. Thus, Fig. 12 shows that CL4 has the highest optical transmittance and therefore optimal optical properties.

[0030] Fig. 13 shows the antimicrobial properties of the contact lenses prepared at various dopamine PL ratios. Fig. 13A shows the bacterial viability, Fig. 13B shows the cytotoxicity of the coated lenses for immortalized human conjunctival epithelial cell lines (IOBA) and Fig. 13C shows the cytotoxicity of human corneal fibroblasts, after being exposed to the inventive contact lenses for 24 hours. Thus, Fig. 13 shows that CL4 has the optimum broad spectrum antimicrobial properties and biocompatibility for human conjunctival epithelial cells and human corneal stromal fibroblasts.

[0031] Fig. 14 is a graph showing the durability of antimicrobial contact lens (CL4) to leaching against S. aureus and P. aeruginosa strains. Fig. 14 shows that ePL-coated lenses retained the antimicrobial activity against both the bacterial strains even after 45 days of immersion in PBS.

[0032] Fig. 15 shows the antimicrobial durability of the contact lenses. Fig. 15A is a representative slit lamp biomicroscopy image of the rabbit cornea implanted with uncoated and antimicrobial coated contact lenses (CL4), and Fig. 15B is a graph showing the intraocular pressure after implanting the uncoated or antimicrobial coated (CL4) contact lenses. Fig. 15 shows that eyes inserted with CL0 or CL4 did not have any signs of corneal oedema, perforation or neovascularization after continuous application of the lenses for five days.

[0033] Fig. 16 shows the biocompatibility of the contact lenses. Fig. 16A and 16B are AS-OCT images showing the corneal thickness after implanting uncoated and antimicrobial coated contact lenses, respectively, and Fig. 16C is a graph showing the change in corneal thickness after implanting the contact lenses. Fig. 16 shows that intraocular pressure (IOP) measurements and central corneal thickness remained identical for both lens inserted eyes.

DETAILED DESCRIPTION

[0034] Microbial keratitis (MK), the microbial infection of the cornea, is the leading cause of ocular morbidity and blindness globally. Ophthalmic device hygiene has become an important concern in the developing world due to the increased incidents on ophthalmic device-related infections, despite the improvement in the ophthalmic device materials. “Ophthalmic”, for the purposes of this disclosure, means“pertaining to the eye”. In recent years, a number of strategies have been reported describing the covalent functionalization of ophthalmic devices with antimicrobial peptides to prevent implant-related infections. However, covalent functionalization of ophthalmic devices requires complex modification of the surface of the device or of the antimicrobial peptides or compound. In view of the above problem, there is a need to provide an alternative biocompatible ophthalmic device and an alternative method to manufacture said devices.

[0035] Oxidative polymerization of catecholamine is a versatile approach for material- independent surface coatings as well as covalent or non-covalent functionalization of the substrates with metal ions, antibiotics, peptides, and macromolecules which have inherent antimicrobial properties. The utility of polydopamine-coating and subsequent functionalization of titanium implant with antimicrobial peptide in averting the microbial colonization of S. aureus and P. aeruginosa for an extended period of time in an alkali burn injury model has been demonstrated.

[0036] In response to the problem above and in view of the versatility of oxidative polymerization of catecholamine, an alternative biocompatible ophthalmic device has been developed. Thus, in one aspect, the present disclosure provides a biocompatible ophthalmic device comprising: a core material; a first component which is coating the surface of the core material; and a second component which is linked to the first component by a bond; wherein the first component comprises cross-links of at least one catecholamine compound and the second component comprises at least one antimicrobial peptide and/or at least one antimicrobial polymer. The first component and the second component may coat the surface of the core material or may form a coat on the surface of the core material. As used herein the term“coat” or“coating” refers to a layer that at least partially covers the surface of a core material. In one example, the coat may cover at least 50%, 60%, 70%, 80%, 90%, or 100% of the core material. The core material may be connected to the first component by a chemical bond and the first component may be connected to the second component by a chemical bond. In one example, the chemical bond connecting the first and the second component may be a covalent bond. In one example, the chemical bond connecting the first and the second component may be a non-covalent bond.

[0037] In one example, the core material is non-covalently linked to the first component and the second component is covalently linked to the first component. In one example, the core material is non-covalently linked to the first component and the second component is non-covalently linked to the first component. In another example, the first component is covalently linked to the core material and the second component is non-covalently linked to the first component. In another example, the first component and second component are non- covalently linked to the core material. As used herein, the term“covalently linked” refers to components that are connected to each other via a covalent bond. As commonly used in the art, the term“covalent bond” refers to a chemical bond that involves the sharing of electron pairs between atoms. As used herein, the term“non-covalently linked” refers to components that are connected to each other via non-covalent interaction. Examples of non-covalent interactions may include but are not limited to electrostatic interaction (e.g. ionic interaction, hydrogen bonding, halogen bonding, and the like), Van der Waals forces (e.g. dipole-dipole interaction, dipole-induced dipole interaction, London dispersion forces, and the like), 71- effects (e.g. p-p interactions, cation-71; and anion-p interactions, polar-p, and the like), hydrophobic effects, and the like.

[0038] As the device described in the present disclosure is an ophthalmic device or a device which is used on the eyes or in relation with the eyes, the device must be biocompatible. As used herein, the term “biocompatible” refers to materials that are compatible with living tissue and/or a living system by not being toxic, injurious, or physiologically reactive, and/or not causing immunological rejection. The biocompatibility of a material can be determined using any method known in the art. In one example, a biocompatible material is a cytocompatible material and is not cytotoxic. The biocompatibility of a material can be determined using any method known in the art. As depicted for example in Fig. 8, in one example, the cytotoxicity of a material can be determined using lactate dehydrogenase (LDH) membrane integrity assay towards various cells. The cells may include but are not limited to epithelial cells (e.g. hTCEpi), stromal cells (e.g. hCSFb), and the like.

[0039] As described herein, the biocompatible ophthalmic device of the present disclosure comprises a core material. As used herein, the term“core material” refers to material that forms the uncoated ophthalmic device. In one example, the core material may include, but are not limited to, hydrogel, poly(HEMA) hydrogels, silicone hydrogel, metals (such as platinum, silver, copper, titanium, gold, palladium, and the like), sapphire (Al₂0₃), quartz, stainless steel, NiTi, silicon, polymer (such as Carbothane® Tecoflex®, polycarbonate, polyethylene terephthalate (PET), poly(styrene), polydimethysiloxane (PDMS), and the like), Acrylate/Methacylate Copolymer, glass, silicon nitride, and the like. A person skilled in the art is aware that Tecoflex® is a family of medical grade aliphatic polyether polyurethanes and Carbothane® is a family of aliphatic and aromatic polycarbonate-based thermoplastic polyurethanes. The generic name of Carbothane® is Aliphatic/Aromatic Acrylic -Polyester Polyurethane. For the purposes of this disclosure,“hydrogel” refers to a macromolecular polymer gel constructed of a network of crosslinked polymer chains. It is a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. Three-dimensional solids result from the hydrophilic polymer chains being held together by cross-links. Because of the inherent cross-links, the structural integrity of the hydrogel network does not dissolve from the high concentration of water.

[0040] The“core material” as defined above may not be further modified or treated both chemically or physically. That is, the“core material” is used as-is, without further chemical or physical modification or treatment. A person skilled in the art is aware that when the ophthalmic device is optically transparent or requires optical transparency in order to function, the core material may include, but are not limited to, hydrogel, poly(HEMA) hydrogels, silicon hydrogel, Acrylate/Methacylate Copolymer, glass, and the like. As used herein, the term“optically transparent” or“having optical transparency” refers to the physical property of allowing light to pass through the material without being scattered. In one example, the ophthalmic device that is optically transparent or requires optical transparency in order to function is selected from the group consisting of contact lens, bandage contact lens, intraocular lens, and the like.

[0041] In one example, wherein when the core material is a hydrogel, silicon hydrogel, glass, and the like, the material is not pre-treated with 1 -ethyl-3 -(3 -dimethylaminopropyl) carbodiimide hydrochloride (EDC). Treatment with l-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) is known in the art to allow covalent binding of antimicrobial peptide on the surface of lenses. Without wishing to be bound by theory, the core material of the present disclosure does not require pretreatment (such as pretreatment using l-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)) because the second component (comprising the at least one antimicrobial peptide and/or at least one antimicrobial polymer) forms a chemical bond to the first component (comprising the cross links of at least one catecholamine compound) and the second component does not directly bind to the core material. The first component itself can readily cross-links and coat the surface of the core material without requiring pre-treatment of the core material. In one example, the core material is a hydrogel. In one example, wherein when the core material is a hydrogel, the hydrogel may include, but are not limited to, bufilcon A, epsifilcon A, etafilcon A, focofilcon A, methafilcon A, methafilcon B, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ocufilcon F, perfilcon A, phemfilcon A, tetrafilcon B, vifilcon A, and the like. In one example, the hydrogel is etafilcon A. The principal monomers composing Etafilcon A are poly-2-hydroxyethylmethacrylate (HEMA) and Methacrylic acid (MA). [0042] Further to the above, besides comprising a core material, the biocompatible ophthalmic device of the present disclosure comprises a first component. The first component comprises cross-links of at least one catecholamine compound. The term“cross-link” or “cross-linking” or“cross-linked” as used herein refers to any type of chemical bond that connects or links one catecholamine compound to the other. As used herein and as commonly known in the art, the term“catecholamine” or“catecholamine compound” refers to a

compound comprising at least one catechol group

one amine group

F¾

(e.g.

wherein Ri, R₂, and R₃ independently correspond to chemical substituents). Non-limiting examples of “catecholamine” or“catecholamine compound” may include but are not limited to (S)-2-Amino-3-(3,4- dihydroxyphenyl)propanoic acid (or L-3,4-dihydroxyphenylalanine or Levodopa), (R)-2- Amino-3-(3,4-dihydroxyphenyl)propanoic acid (or D-3,4-dihydroxyphenylalanine or Dextrodopa), L-3,4-dihydroxyphenylalanine methyl ester, D-3,4-dihydroxyphenylalanine methyl ester, 4-(2-aminoethyl)benzene-l,2-diol (or 3,4-dihydroxyphenethylamine or Dopamine), 4-[(lR)-2-amino-l-hydroxyethyl]benzene-l,2-diol (or Norepinephrine or Noradrenaline), 4-[(lS)-2-amino-l-hydroxyethyl]benzene-l,2-diol, (R)-4-(l-Hydroxy-2- (methylamino)ethyl)benzene-l,2-diol (or Epinephrine or Adrenaline), (S)-4-(l-Hydroxy-2- (methylamino)ethyl)benzene-l,2-diol, Adrenalone, Carbidopa, Colterol, DimethylDOPA, Dioxifedrine, Dioxethedrin, 5 -hydroxy dopamine, Dobutamine, Dopexamine, Droxidopa, a- methylnorepinephrine (or alpha-methylnorepinephrine or Corbadrine or Nordefrin), Ethylnorepinephrine, Etilevodopa, Isoetharine, Hexoprenaline, N-methyladrenalone, Norbudrine, Oxidopamine, and the like. The structures of the non-limiting examples of “catecholamine” or“catecholamine compound” are shown on Table 1 below:

Table 1. Structures of“catecholamine” or“catecholamine compound”. [0043] In one example, the catecholamine compound is dopamine (or 4-(2- aminoethyl)benzene-l,2-diol or 3,4-dihydroxyphenethylamine or

norepinephrine (4-[(lR)-2-amino-l-hydroxyethyl]benzene-

l,2-diol; Noradrenaline;

[0044] Catecholamines such as dopamine and norepinephrine are capable of self polymerization. When dopamine self -polymerizes, it forms a polydopamine (pDA) coating, whereby the phenolic hydroxyl groups on dopamine are partially oxidized to quinone groups. [0045] In addition to the examples of catecholamine listed above, the“catecholamine” or a“catecholamine compound” may be represented by a structure according to Formula I

wherein each of Ri, R₃, R4 and R5 is independently selected from the group consisting of a thiol, a primary amine, a secondary amine, a nitrile, an aldehyde, an imidazole, an azide, a halide, a hydrogen, a hydroxyl, a carboxylic acid, an aldehyde, an ester; wherein R₂ is a primary amine or a secondary amine; and wherein x ranges from 0 to 10 and wherein y ranges from 0 to 10, provided that x or y is at least 1. In one example, one of Ri or R₄ is a halide, a hydroxyl, or a thiol, and one of R₃ or R5 is a hydrogen atom. In one example, x+y is at least 2. In one example, x+y is at least 3. In one example, x is 1, y is 1, Ri is a hydroxyl, R₂ is a primary amine, and each of R₃, R₄ and R5 are hydrogen atoms. In one example, x is 1, y is 1, Ri is a hydroxyl, R₂is a secondary amine, and each of R₃, R₄ and R5 are hydrogen atoms. In one example, x is 1, y is 1, R₂ is a primary amine, and each of Ri, R₃, R₄ and R5 are hydrogen atoms. In one example, x is 1, y is 1, R₄ is an ester, R₂ is a primary amine, and each of Ri, R₃ and R5 are hydrogen atoms. In one example, x is 1, y is 1, R₄ is a carboxylic acid, R₂is a primary amine, and each of Ri, R₃ and R5 are hydrogen atoms. In one example, the hydroxyls of the phenyl moiety are positioned at the 3 and 4 positions of the phenyl group relative to the side chain. Non-limiting examples of “catecholamine” or “catecholamine compound” that are represented by a molecule according to Formula I may include but are not limited to (S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid (or L-3,4- dihydroxyphenylalanine or Levodopa), (R)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid (or D-3,4-dihydroxyphenylalanine or Dextrodopa), L-3,4-dihydroxyphenylalanine methyl ester, D-3,4-dihydroxyphenylalanine methyl ester, 4-(2-aminoethyl)benzene-l,2-diol (or 3,4- dihydroxyphenethylamine or Dopamine), 4-[(lR)-2-amino-l-hydroxyethyl]benzene-l,2-diol (or Norepinephrine or Noradrenaline), 4-[(lS)-2-amino-l-hydroxyethyl]benzene-l,2-diol,

(R)-4-(l-Hydroxy-2-(methylamino)ethyl)benzene-l,2-diol (or Epinephrine or Adrenaline),

(S)-4-(l-Hydroxy-2-(methylamino)ethyl)benzene-l,2-diol, and the like.

[0046] Further to the above, besides comprising a core material and a first component, the biocompatible ophthalmic device of the present disclosure comprises a second component. In one example, the second component may be an antimicrobial peptide, or an antimicrobial polymer, or any combination thereof. Because the antimicrobial peptide, or the antimicrobial polymer, or any combination thereof is a component of a biocompatible ophthalmic device, a person skilled in the art is aware that the antimicrobial peptide, or the antimicrobial polymer, or any combination thereof is not cytotoxic. As used herein, the term“antimicrobial” refers to materials that are able to reduce the viability and/or inhibit the growth of microorganism. “Viability”, for the purposes of this disclosure refers to the ability of the microorganism to survive or live successfully, and can be measured by methods known in the art, or by the exemplary method for testing viability as described in the experimental section (see paragraph [0085]). A material having antimicrobial property may reduce the viability and/or the growth of a microorganism by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 100% when compared to a control, or by a range from 10% to 100%, from 10% to 25%, from 25% to 50%, from 10% to 50%, from 50% to 75%, from 75% to 100%, from 50% to 100% when compared to a control.

[0047] In order for the antimicrobial peptide of the second component to be able to be linked to the first component comprising cross-links of at least one catecholamine compound, the antimicrobial peptide must comprise certain amino acid residue. Therefore, in one example, the antimicrobial peptide may be a peptide comprising at least one lysine residue (amino group), or a peptide comprising at least one cysteine residue (thiol group), or a peptide comprising at least one histidine residue (imidazole group). Non limiting example of the antimicrobial peptide comprising at least one lysine residue (amino group) may include, but are not limited to RGRKVVRRKK (SEQ ID NO.: 1) (monomer), RGRKVVRRKKRRVVKRGR (SEQ ID NO.: 2) (linear retrodimer), [( AGRKVVRR)₂K] ₂K (SEQ ID NO.: 5), [(RARKVVRR)₂K]₂K (SEQ ID NO.: 6), [(RGAKVVRR)₂K]₂K (SEQ ID NO.: 7), [(RGRAVVRR)₂K]₂K (SEQ ID NO.: 8), [(RGRKA VRR)₂K] ₂K (SEQ ID NO.: 9), [(RGRKVARR)₂K]₂K (SEQ ID NO.: 10), [(RGRKVVAR)₂K]₂K (SEQ ID NO.: 11), [(RGRKVVRA)₂K]₂K (SEQ ID NO.: 12); [(RGAA VVRR)₂K] ₂K (SEQ ID NO.: 13), [(RGRKVVAA)₂K]₂K (SEQ ID NO.: 14), [(RGAKA VRR)₂K] ₂K (SEQ ID NO.: 15),

[(RGRKAARR)₂K]₂K (SEQ ID NO.: 16), [(RGAAA VRR)₂K] ₂K (SEQ ID NO.: 17),

[(RGAKAARR)₂K]₂K (SEQ ID NO.: 18), [(RGRAAARR)₂K]₂K (SEQ ID NO.: 19),

[(RGAAAARR)₂K]₂K (SEQ ID NO.: 20), [(RGRKAAAA)₂K]₂K (SEQ ID NO.: 21);

[(GRKVVRR)₂K]₂KK (SEQ ID NO.: 22), [(RKVVRR)₂K]₂K (SEQ ID NO.: 23), [(KVVRR)₂K]₂K (SEQ ID NO.: 24), [(VVRR)₂K]₂K (SEQ ID NO.: 25), [(VRR)₂K]₂K (SEQ ID NO.: 26), [(RR)₂K]₂K (SEQ ID NO.: 27), [(R)₂K]₂K (SEQ ID NO.: 28); [(VRGRVRKR)₂K]₂K (SEQ ID NO.: 29) (scrambled pAMP B4010 DK), [(AGRKVVRR)₂K]₂KK (SEQ ID NO. 30), [(RARKVVRR)₂K]₂KK (SEQ ID NO. 31),

[(RGAKVVRR)₂K]₂KK (SEQ ID NO. 32), [(RGRAVVRR)₂K]₂KK (SEQ ID NO. 33),

[(RGRKAVRR)₂K]₂KK (SEQ ID NO. 34), [(RGRKVARR)₂K]₂KK (SEQ ID NO. 35),

[(RGRKVVAR)₂K]₂KK (SEQ ID NO. 36), [(RGRKVVRA)₂K]₂KK (SEQ ID NO. 37);

[(RGAAVVRR)₂K]₂KK (SEQ ID NO. 38), [(RGRKVV AA)₂K] ₂KK (SEQ ID NO. 39),

[(RGAKAVRR)₂K]₂KK (SEQ ID NO. 40), [(RGRKAARR)₂K]₂KK (SEQ ID NO. 41),

[(RGAAAVRR)₂K]₂KK (SEQ ID NO. 42), [(RGAKAARR)₂K]₂KK (SEQ ID NO. 43),

[(RGRAAARR)₂K]₂KK (SEQ ID NO. 44), [(RGAAAARR)₂K]₂KK (SEQ ID NO. 45),

[(RGRKAAAA)₂K]₂KK (SEQ ID NO. 46); [(GRKVVRR)₂K]₂KK (SEQ ID NO. 47), [(RKVVRR)₂K]₂KK (SEQ ID NO. 48), [(KVVRR)₂K]₂KK (SEQ ID NO. 49), [(VVRR)₂K]₂KK (SEQ ID NO. 50), [(VRR)₂K]₂KK (SEQ ID NO. 51), [(RR)₂K]₂KK (SEQ ID NO. 52), [(R)₂K]₂KK(SEQ ID NO. 53); [( VRGR VRKR)₂K] ₂KK (SEQ ID NO. 54) (scrambled bAMP B4010), (RGRKVVRR)₂KKK (SEQ ID NO. 55) (bAMP B2088),

[(RGRKVVRR)2K]₂KK (SEQ ID NO. 56) (bAMP B4010), and the like. In one example, the antimicrobial peptide comprising at least one lysine residue is [(RGRKVVRR)₂K]₂K (SEQ

ID NO.: 56) (or

or bAMP B4010).

[0048] In order for the antimicrobial polymer of the second component to be able to be linked to the first component comprising cross-links of at least one catecholamine compound, the antimicrobial polymer must comprise certain functional groups. Therefore, in one example, the antimicrobial polymer may be a polymer comprising at least one amino group, or a polymer comprising at least one thiol group, or a polymer comprising at least one imidazole group. Non limiting example of the antimicrobial polymer comprising at least one amino group may include, but are not limited to, Poly-L-Lysine, Poly-D-Lysine, e-poly-L- Lysine, linear Polyethylenimine (linear PEI), branched Polyethylenimine (branched PEI), and the like. e-poly-L-lysine has the following structure; wherein n is any integer in the range of 4 to 40. n is preferably in the range of 20 to 40 or 25 to 35. n is an integer selected from 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35. e-poly-L-lysine may have an average molecular weight in the range of about 3000 to about 5000, about 3000 to about 4000 or about 4000 to about 5000. e-poly-L-lysine may have an average molecular weight of about 4000. In one example, the biocompatible ophthalmic device described herein may include but are not limited to optical prosthetic device, intraocular lens, artificial eye, contact lens, bandage contact lens, device care box, ophthalmic surgical device, and the like. As used herein, the term“device care box” refers to containers for storing, placing, or holding ophthalmic devices. As used herein, the term “ophthalmic surgical device” refers to devices for use in ophthalmic surgery. The ophthalmic surgical devices may include, but are not limited to, needles, needle holders, forceps,

Chalazion scoop, diamond knife, entropion clamp, Nettleship's punctum dilator, cystitome, wire vectis, irrigating vectis, canula, Lang's lacrimal dissector with scoop, rougine, retractor, bone punch, evisceration spoon or scoop, lid plate, Bowmen's discission needle, knives, scalpels, surgical scissors, Bowman's lacrimal probe, Lens expressor, McNamar's spoon, iris repositor, Sinsky's hook intraocular lens dialer, Strabismus hook, foreign body spud and needle, Elliot's trephine with handle, Castroveijo's corneal trephine, and the like. The ophthalmic surgical devices may include, but are not limited to, Chalazion scoop, entropion clamp, Nettleship's punctum dilator, cystitome, wire vectis, irrigating vectis, Lang's lacrimal dissector with scoop, rougine, evisceration spoon or scoop, lid plate, Bowmen's discission needle, Bowman's lacrimal probe, Lens expressor, McNamar's spoon, Iris repository, Sinsky's hook intraocular lens dialer, Strabismus hook, foreign body spud and needle, Elliot's trephine with handle, Castroveijo's comeal trephine, and the like.

[0049] In one example, the biocompatible ophthalmic device described herein may also be a contact lens or a bandage contact lens. As commonly known in the art, a contact lens or a bandage contact lens can be characterized based on its diopter value. As used herein, the term “diopter value” refers to a unit of measurement of the optical power of a lens, which is equal to the reciprocal of the focal length measured in meters (that is, l/meters). In order for a contact lens or a bandage contact lens to be functional, the contact lens or the bandage contact lens of the present disclosure has to maintain the diopter value of the core material, which is the uncoated contact lens or the uncoated bandage contact lens. Thus, in one example, the contact lens or the bandage contact lens has a diopter value within the range of - 0.5 to +0.5 diopters, or -0.45 to +0.45 diopters, or -0.4 to +0.4 diopters, or -0.35 to +0.35 diopters, or -0.3 to +0.3 diopters, or -0.25 to +0.25 diopters, or -0.2 to +0.2 diopters from the diopter value of the core material. In one example, the contact lens or the bandage contact lens has a diopter value within the range of -0.2 to +0.2 diopters from the diopter value of the core material.

[0050] The biocompatible ophthalmic device described herein comprises at least one antimicrobial peptide and/or at least one antimicrobial polymer. Therefore, the biocompatible ophthalmic device of described herein has antimicrobial property and thus it is able to affect the viability of a microorganism. In one example, the microorganism is a pathogenic microorganism. The microorganism may include, but is not limited to, bacteria, fungi, archaea, protists, viruses, and the like. In one example, the first component and the second component of the biocompatible ophthalmic device described herein reduces the viability of a bacterium or a fungus. In one example, the first component and the second component of the biocompatible ophthalmic device described herein prevents the adhesion of a bacterium or a fungus to said device. For the purposes of this disclosure“adhesion” refers to the tendency of a bacterium or fungus to cling to the surface of the ophthalmic device. Without wishing to be bound by theory, because the viability of the bacterium or fungus is reduced and because the bacterium or the fungus may not adhere to the biocompatible ophthalmic device, the formation of biofilm by the fungus or the bacteria is inhibited. As used herein, the term “biofilm” refers to any group of microorganisms in which cells stick to each other and often adhere to a surface. Therefore, as used herein, the term“anti-biofilm” refers to materials that are able to inhibit the formation of biofilm. Without wishing to be bound by theory, the inhibition of the biofilm formation may be caused by cell shrinkage, loss of cell membrane integrity, and the like. A material having an anti-biofilm property may reduce the size of the biofilm formed on a surface of a device by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 100% when compared to a control, or by a range from 10% to 100%, from 10% to 25%, from 25% to 50%, from 10% to 50%, from 50% to 75%, from 75% to 100%, from 50% to 100% when compared to a control.

[0051] The microorganism that may be affected by the antimicrobial property of the biocompatible ophthalmic device described herein may be a bacterium. In one example, the bacterium may be a gram positive bacterium or a gram negative bacterium. Non limiting example of the bacterium may include, but is not limited to, Acetobacter spp., Acinetobacter spp., Actinomyces spp., Agrobacterium spp., Azorhizobium spp., Azotobacter spp., Anaplasma spp., Bacillus spp., Bacteroides spp., Bartonella spp., Bordetella spp., Borrelia spp., Brucella spp., Burkholderia spp., Calymmatobacterium spp., Campylobacter spp., Chlamydia spp., Chlamydophila spp., Clostridium spp., Corynebacterium spp., Coxiella spp., Ehrlichia spp., Enterobacter spp., Enterococcus spp., Escherichia spp., Francisella spp., Fusobacterium spp., Gardnerella spp., Haemophilus spp., Helicobacter spp., Klebsiella spp., Lactobacillus spp., Lactococcus spp., Legionella spp., Listeria spp., Methanobacterium extroquens, Microbacterium multiforme, Micrococcus luteus, Moraxella catarrhalis, Mycobacterium spp., Mycoplasma spp., Neisseria spp., Pasteurella spp., Peptostreptococcus spp., Porphyromonas spp., Pseudomonas spp., Rhizobium spp., Rickettsia spp., Rochalimaea spp., Rothia spp., Salmonella spp., Serratia spp., Shigella spp., Staphylococcus spp., Stenotrophomonas spp., Streptococcus spp., Treponema spp., Vibrio spp., Wolbachia, Yersinia spp, and the like. Non limiting example of the bacterium may include, but is not limited to, Pseudomonas spp., Staphylococcus spp., Serratia spp., and the like. In one example, the bacterium may be MRSA (Methicillin-resistant Staphylococcus aureus), or Staphylococcus aureus, or Pseudomonas aeruginosa. In one example, the MRSA may be MRSA DM21455 or MRSA DM9809R. In one example, the Staphylococcus aureus may be Staphylococcus aureus 4001R or Staphylococcus aureus 4400R. In one example, the Pseudomonas aeruginosa may be Pseudomonas aeruginosa ATCC9027 or Pseudomonas aeruginosa DM23155.

[0052] The microorganism that may be affected by the antimicrobial property of the biocompatible ophthalmic device described herein may be a fungus. Non limiting example of the fungus may include but are not limited to Absidia spp., Ajellomyces spp., Arthroderma spp., Aspergillus spp., Blastomyces spp., Candida spp., Cladophialophora spp., Coccidioides spp., Cryptococcus spp., Cunninghamella spp., Epidermophyton spp., Exophiala spp., Filobasidiella spp., Fonsecaea spp., Fusarium spp., Geotrichum spp., Histoplasma spp., Hortaea spp., Issatschenkia spp., Madurella spp., Malassezia spp., Microsporum spp., Microsporidia spp., Mucor spp., Nectria spp., Paecilomyces spp., Paracoccidioides spp., Penicillium spp., Pichia spp., Pneumocystis spp., Pseudallescheria spp., Rhizopus spp., Rhodotorula spp., Scedosporium spp., Schizophyllum spp., Sporothrix spp., Trichophyton spp., Trichosporon spp, and the like. In one example, the fungus may be Fusarium spp. [0053] In another aspect, the present disclosure provides a method of preventing, suppressing and/or treating an ophthalmic infection in an eye of a subject comprising the placement of a device as disclosed herein in the eye of the subject. In yet another aspect, the present disclosure provides a device as disclosed herein for use in preventing, suppressing and/or treating an ophthalmic infection in a subject. The ophthalmic device may be worn by a subject with an uninfected eye to prevent the development of an ophthalmic infection, by a subject with an infected eye to suppress the symptoms of an ophthalmic infection, or by a subject with an infected eye to treat the symptoms of an ophthalmic infection. Non-limiting example of an ophthalmic infection may include, but are not limited to, blepharitis, microbial keratitis, dacryocystitis, orbital cellulitis, and the like. In one example, the ophthalmic infection is microbial keratitis. As used herein, the term “microbial” refers to any microorganism capable of causing disease or infection in a host or a subject. Collectively, the term“microbial” refers to bacteria, viruses, protists (including certain algae) and fungi. For example, when used in conjunction with the term“keratitis”, the term“microbial keratitis” refers to keratitis caused by any of the microorganisms listed above. That is to say, keratitis can be viral keratitis, bacterial keratitis, fungal keratitis, parasitic keratitis or amoebic keratitis. Thus, in one example, the keratitis is bacterial keratitis.

[0054] In addition to finding an alternative biocompatible ophthalmic device, an alternative method to manufacture the alternative biocompatible ophthalmic device has also been found. Thus, in yet another aspect, the present disclosure provides a method of manufacturing a biocompatible ophthalmic device disclosed herein, wherein the method comprises contacting a core material with a mixture comprising at least one catecholamine compound, at least one antimicrobial peptide and/or at least one antimicrobial polymer, and a biocompatible buffer to allow the formation of a coat on the surface of the core material; and removing excess first component, second component, and biocompatible buffer. It has been surprisingly found that a mixture comprising at least one catecholamine compound, at least one antimicrobial peptide and/or at least one antimicrobial polymer, and a biocompatible buffer is effective for coating ophthalmic devices because said mixture provides for a more uniform coating and improves the stability of the coat. The first component and the second component form a coat on the surface of the core material. The first component may form a coat on the surface of the core material and the second component may form a link to the first component by a bond. The bond may be covalent or non-covalent. The second component may be present between the core material and the first component, on the outer surface of the first component, or intermingled in the same layer as the first component. If the second component is present on the outer surface of the first component, then the first component may form a first layer around the core material and the second component may form a second layer around the first component. If the second component is intermingled in the same layer as the first component, then the first component and second component may form a single layer comprised of a mixture of the first component and the second component. As used herein the term“coat” refers to a layer that covers all around a core material. In one example, the coat may cover at least 50%, 60%, 70%, 80%, 90%, or 100% of the core material.

[0055] As used herein, the term“contacting” refers to any suitable method of bringing the core material into contact with a mixture comprising the first component and the second component. In one example, the method may include spraying, submerging, and the like. In one example, the coat may cover at least 50%, 60%, 70%, 80%, 90%, or 100% of the core material.

[0056] During the development of the manufacturing method of the biocompatible device, it was found that the buffer used should not leave a residue on the biocompatible ophthalmic device. In one example, the biocompatible buffer used in the manufacturing method is an inorganic buffer. Non-limiting examples of the inorganic buffer may include but are not limited to phosphate buffer, carbonate buffer (or sodium bicarbonate or NaHC0₃ buffer), ammonium bicarbonate (or NH4HCO3), and the like. In one example, the inorganic buffer is carbonate buffer (or sodium bicarbonate or NaHC0₃ buffer).

[0057] Further to the above, it was surprisingly found that certain concentrations of catecholamine compounds assisted in providing a desired diopter value in the manufacture of the biocompatible ophthalmic device disclosed herein. Thus, in one example, the concentration of the catecholamine compound in the mixture is from 0.10 mg/mL to 0.15 mg/mL, or from 0.15 mg/mL to 0.20 mg/mL, or from 0.20 mg/mL to 0.25 mg/mL, or from 0.25 mg/mL to 0.30 mg/mL, or from 0.30 mg/mL to 0.35 mg/mL, or from 0.35 mg/mL to 0.40 mg/mL, or from 0.40 mg/mL to 0.45 mg/mL, or from 0.45 mg/mL to 0.50 mg/mL, or from 0.10 mg/mL to 0.50 mg/mL, or from 0.15 mg/mL to 0.45 mg/mL, or from 0.20 mg/mL to 0.40 mg/mL, or from 0.25 mg/mL to 0.35 mg/mL, or from 0.25 mg/mL to 0.30 mg/mL, or about 0.20 mg/mL, or about 0.21 mg/mL, or about 0.22 mg/mL, or about 0.23 mg/mL, or about 0.24 mg/mL, or about 0.25 mg/mL, or about 0.26 mg/mL, or about 0.27 mg/mL, or about 0.28 mg/mL, or about 0.29 mg/mL, or about 0.30 mg/mL. In one example, the concentration of the catecholamine compound in the mixture is about 0.25 mg/mL. The inventors have surprisingly found that when the concentration of the catecholamine compound in the mixture is higher than 0.5 mg/mL and/or the step of contacting a core material with the mixture comprising at least one catecholamine compound is performed for a long period of time and/or in the absence of agitation, the core material may become colored or discolored, the core material surface may be covered with precipitates, the core material may have opaque surface, the core material may have non-uniform coating, and/or the core material may no longer be clear or optically transparent (Fig. 11). Additionally, it was surprisingly found that certain ratios of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture assist in providing a desired diopter value during the manufacturing of the biocompatible ophthalmic device. Therefore, in one example, the ratio of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture is from 1:1 to 1:1.5, or from 1:1.5 to 1:2, or from 1:2 to 1:2.5, or from 1:2.5 to 1:3, or from 1:3 to 1:3.5, or from 1:3.5 to 1:4, or from 1:4 to 1:4.5, or from 1:4.5 to 1:5, or from 1:1 to 1:5, or from 1:1 to 1:4.5, or from 1:1 to 1:4, or from 1:1.5 to 1:3.5, or from 1:1.5 to 1:3, or from 1:2 to 1:3, or from 1:2 to 1:2.5, or about 1:1, or about 1:1.5, or about 1:2, or about 1:2.5, or about 1:3, or about 1:3.5, or about 1:4, or about 1:4.5, or about 1:5, or about 1:5.5, or about 1:6, or about 1:6.5, or about 1:7, or about 1:7.5, or about 1:8, or about 1:8.5, or about 1:9 or about 1:9.5 or about 1:10.

[0058] In the present disclosure, it was found that high optical transparency, clarity and low coloration of the core material was achieved even if low concentrations of the first component and second component were used to coat the core material.

[0059] In another aspect, the present disclosure provides a kit for preparing a biocompatible ophthalmic device as disclosed herein, the kit comprising: a core material; and a mixture comprising: a first component comprising at least one catecholamine compound; a second component comprising at least one antimicrobial peptide and/or at least one antimicrobial polymer and a biocompatible buffer. To prepare the ophthalmic device, the core material must be immersed in the mixture, in accordance with the method of manufacturing the biocompatible ophthalmic device as disclosed herein.

[0060] As used in this application, the singular form“a,”“an,” and“the” include plural references unless the context clearly dictates otherwise. For example, the term “a component” includes a plurality of components, including mixtures and combinations thereof. [0061] As used herein, the terms“increase” and“decrease” refer to the relative alteration of a chosen trait or characteristic in a subset of a population in comparison to the same trait or characteristic as present in the whole population. An increase thus indicates a change on a positive scale, whereas a decrease indicates a change on a negative scale. The term“change”, as used herein, also refers to the difference between a chosen trait or characteristic of an isolated population subset in comparison to the same trait or characteristic in the population as a whole. However, this term is without valuation of the difference seen.

[0062] As used herein, the term“about” in the context of concentration of a stated value means +/- 5% of the stated value, or +/- 4% of the stated value, or +/- 3% of the stated value, or +/- 2% of the stated value, or +/- 1% of the stated value, or +/- 0.5% of the stated value.

[0063] Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0064] The embodiments illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms "comprising", "including", "containing", etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the disclosure. Thus, it should be understood that although the present disclosure has been specifically disclosed by preferred embodiments and optional features, modification and variation of the embodiments herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this disclosure.

[0065] The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0066] Other embodiments are within the following claims and non- limiting examples. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

EXAMPLES

[0067] The method described in the present disclosure will provide a one-step strategy to prepare antimicrobial contact lenses that not only retain their antibacterial efficiency against different bacterial strains ( S . aureus, MRSA, P. aeruginosa ) for 2 weeks but also inhibit the microbial adhesion and biofilm formation on the contact lens surface. bAMP based coatings over the contact lenses is found to be safe or biocompatible with the ocular surface. The functional (such as optical power, wearer’s perception to different colors, and the like) and surface properties (such as wettability, surface roughness, and the like) of the contact lenses are also found to be unaffected by the invented antimicrobial coatings. The developed method to design polydopamine-mediated antimicrobial coatings may also be used to protect all types of contact lenses from microbial contamination for extended periods of time. This approach may be further extended to designing antimicrobial coatings for other medical devices such as catheters, dental implants, vascular grafts, mechanical heart valves, and the like.

[0068] Appearance of slight brown coloration on the coated contact lenses is one of the main challenges related to the development methodology which affects the wearer’s ability to see white color, however, it did not affect the clarity of the contact lens and the wearer’s perception of other colors. To overcome this, there are a few alternative strategies to explore. One of these is to reduce the concentration of dopamine, which actually polymerize during the coating process and contributes to the brown coloration. Another strategy is to replace dopamine with other colorless multifunctional coating agents such as norepinephrine, and the like.

[0069] EXAMPLE 1: MATERIALS

[0070] Dopamine hydrochloride (DA), hexamethyldisilazane (HMDS), paraformaldehyde, glutaraldehyde, sodium chloride, sodium hydroxide, and phosphate buffer saline (PBS) were purchased from Sigma Aldrich, Singapore. The g-Mangostin (purity: >98%; yMG) was obtained from Chengdu Biopurity Phytochemicals, Ltd., China. Branched antimicrobial peptide (bAMP) B4010 was purchased from M/s. Peptide Mimatopes, Australia. Tris(hydroxymethyl)aminomethane hydrochloride was received from Bio-Rad Laboratories Inc., California, USA. For performing the antimicrobial assays, Mueller Hinton (MH) agar, Mueller Hinton broth and Tryptic Soy broth (TSB) were purchased from Becton, Dockinson and Company (Maryland, USA). All the bacterial strains used in this study, including S. aureus 4001R, S. aureus 4400R, MRSA DM21455, and MRSA DM9808R were clinically isolated strains of the eye, and were received from Pathology department, Singapore General Hospital, Singapore, except multi-drug resistant Pseudomonas aeruginosa and Carbapenem- resistant Enterobacter (CREs) which were obtained from Professor Tim Barkham at Tan Tock Seng Hospital, Singapore and P. aeruginosa ATCC 9027 strain which was purchased from ATCC (American Type Culture Collection) and cultured according to the instructions provided. For fungi, Candida spp. and Fusarium solani were obtained from ATCC (American Type Culture Collection) and cultured according to the instructions provided. For cell culture experiments, human primary corneal stromal fibroblast cells (hCSFb) and Tel om erase-i m m ortal i zed human corneal epithelial cells (hTCEpi) were purchased from ATCC. Human conjunctival epithelial cells (IOBA) were obtained from Margarita Calonge and Yolanda Diebold at the University of Valla-dolid, Valladolid, Spain. Dulbecco’s modified eagle medium (DMEM) and F-12 mixture supplemented with 4-(2-hydroxyethyl)- l-piperazineethanesulfonic acid (HEPES), L-Glutamine and 1% antibiotic antimycotic mixture were obtained from Life technologies holdings Pte. Ltd, Singapore. Serum-free, calcium free keratinocyte culture medium (SFCF-KCM) was received from Dermalife, Lifeline cell technology (Maryland, USA). CytoTox-ONE homogenous membrane integrity assay kit was procured from Promega (Wisconsin, USA). Etalfilcon A contact lenses (Acuvue, Singapore) were purchased in their original packaging, and had a diameter of 14.2 mm, curvature of 8.6 mm and refractive power of -3.00 D. Epsilon poly-L-lysine (sPL) (Mw: -4,000) was purchased from Hefei TNJ Chemical Industry Co Ltd, China and used as received.

[0071] EXAMPLE 2: METHODS

[0072] Optimization of contact lens coating parameters

[0073] Considering the fact that Tris-HCL (pH 8.5) is the most explored chemical medium for the development of polydopamine coatings but also that this buffer solution can be toxic to the ocular tissue even in traces, the coating potential of polydopamine (pDA) was investigated in two buffer solutions, i.e. Tris-HCL (pH 8.5) and NaHC0₃ (pH 8.5) on uncoated contact lens (UCL) surfaces. UV-Visible studies were carried out to validate the development of pDA coating on the contact lens (CL) surface using a UV-vis spectrophotometer (UV1800, Shimadzu Scientific Instruments Inc., Maryland, USA) in the wavelength range of 200-700 nm at 25°C. To generate uniform and homogenous pDA, b AMP-pDA and yMG-pDA coatings on CLs, the effect of varying dopamine concentrations, the dopamine:antimicrobial ratio and coating duration were examined. Etafilcon A contact lenses were selected as the uncoated contact lens as they are readily available and easy to handle during the coating process. The solutions tested to develop different coatings on the CLs are shown in Table 2. For the coating process, fresh CLs were first washed thrice with MilliQ water and soaked in 1 ml of each coating solution (as shown in Table 2) in a 24-well plate with constant shaking at 300 rpm at 37 C for different time durations. The CLs were then washed thrice with MilliQ water to remove any unbound antimicrobials or pDA aggregates. The optimal coating conditions were determined based on the clarity, color and antimicrobial activity of the coated CLs. CLs prepared by the optimized coating conditions were carried forward for further studies.

[0074] Table 2: Different solutions tested for the development of different contact lens coatings.

[0075] Antimicrobial susceptibility testing of B4010 bAMP and yMG [0076] The minimum inhibitory concentrations (MIC) of B4010 bAMP and yMG were determined in two independent duplicates using a microdilution method following the Clinical and Laboratory Standards Institute (CLSI) protocols. Overnight cultured bacterial strains were suspended in MHB at a starting optical density of approximately 0.08 in a flat bottomed microtiter plate. Serial dilutions of bAMP and yMG in MH broth was mixed with the bacterial inoculum to provide the final concentration of 1.56 - 50.00 pg/mL for bAMP and 0.39 - 12.50 pg/mL for yMG, respectively, with a final bacterial density of 10⁵ - 10⁶ CFU/mL in each well. Antibacterial activity was assessed by monitoring the optical density at 600 nm using an Infinite® M200 microplate reader (Tecan Group Ltd, Switzerland) after 24 hours incubation at 37°C. Culture without bAMP/yMG was used as positive control and broth alone or with 50/12.50 pg/mL of bAMP/yMG was served as negative control. The minimum concentration required for the complete inhibition was assessed by both visible observations as well as by measuring the optical density at 600 nm and taken as the MIC. Each experiment was repeated in triplicates.

[0077] Assessment of the antimicrobial properties of the contact lenses and evaluation of their antimicrobial durability

[0078] Antimicrobial properties of the coated contact lenses were evaluated using the microbroth growth inhibition assay. For this, the contact lenses were incubated in 2 mL of MH broth containing bacterial culture (at 0.5 McFarland standards) with final bacterial density of 10⁵-10⁶ CFU/mL for 24 hours at 37 °C. After preparing one-log (10 fold) serial dilutions of the above solutions in PBS, 100 pL of each dilution was pour plated on MH agar plates and incubated for 48 hours at 37 °C. The colony-forming units (CFUs) were counted for l0⁶-fold dilution for different bacterial strains. The reduction factor was estimated using equation,

Rf= log₁₀N_c ^~ log₁₀N_d . Eq. 1 where N_c is the number of viable cells (CFU) in the inoculum containing the control or uncoated contact lens and N_d is the number of viable cells in the inoculum containing coated contact lenses. Antimicrobial activity of various coated contact lenses was expressed in percentage growth inhibition relative to the uncoated contact lens.

[0079] To evaluate the antimicrobial durability of the coated contact lenses, each contact lens was soaked in 1 mL of contact lens solution in 24 well plates at room temperature for 1, 3, 5, 7 and 14 days, respectively. At each time point, the antimicrobial activity of the CL was assessed against MRSA DM21455 and P. aeruginosa DM23155 strains using microbroth growth inhibition assay as described above. The experiments were performed in triplicates and the results were averaged.

[0080] In-Vitro Biocompatibility of the Coated Contact Lenses

[0081] The in-vitro biocompatibility of the coated CLs was assessed using the CytoTox- ONE homogeneous membrane integrity assay kit. The Telomerase-immortalized human comeal epithelial (hTCEpi) cells and Human primary comeal stromal fibroblasts (hCSFb) ocular cells were maintained at 37 °C in a humidified 5% C0₂ incubator in a culture medium containing DMEM/F-15 (1: 1) and SFCF-KCM medium, respectively. The cells were then harvested with trypsin-EDTA from the tissue culture flasks. Both the cells were seeded on uncoated and coated CFs in two separate 24-well plates at the seeding density of approximately 60,000 HCSFb/well and 20,000 hTCEpi/well. After 24 hours of incubation at

37 C, the plates were equilibrated to 25-27 C for 30 minutes. 50 pl of the supernatant was extracted from each well, transferred to a 96-well plate and processed according to manufacturer’s protocol. The fluorescence of the supernatants (l_{ϋCIIί1ϋ IP} = 560 nm, k_CIIIISSKm = 590 nm) was then measured using microplate reader. Media with untreated cells served as negative control while media with cells treated with 1% Triton-X solution served as positive control. The experiments were performed in triplicates and percentage viability was calculated using equation 2,

% Viability 100 . Eq. 2

where F_s, F_p and F_n are the fluorescence of the sample, positive control and negative control respectively. The compound was considered cytotoxic if the percentage viability was less than 70%. The morphology of the cells was also examined under inverted microscope (Eclipse TS 100, Nikon Instruments Inc., New York, USA).

[0082] X-Ray Photoelectron Spectroscopy.

[0083] XPS studies were executed in a Kratos AXIS Ultra VLD (Kratos Analytical Ltd) system using base pressure of approximately 10-9 Torr. Photoemission was induced by Al Ka (1486.71 eV) radiation, as using physical electronics 04-548 dual Mg/Al anode. XPSPEAK 4.1 was used to curve resolve the XPS data after subtracting the Shirley background. The curve resolved spectra were fitted with the minimum number of peaks which are needed to reproduce the spectral features with a 75% Gaussian/25% Lorentzian peak shape using a Gaussian-Lorentzian product function. [0084] Static Contact Angle Measurements

[0085] Surface wettability of the CLs was evaluated using sessile drop method. Four small slits were made at the circumference of each CL before mounting onto a glass coverslip with its convex side facing up. Static contact angle was measured 10 seconds after 3 pL of MilliQ water was placed on the surface of the CL. In the measurement of advancing contact angle, 3 pL of MilliQ water was first deposited to form a drop on the CL surface and then more water was gradually added to the drop until the contact angle did not increase further. In the measurement of receding contact angle, water was slowly withdrawn from that drop until the volume of the drop returned to 3 pL. All the contact angles were measured at room temperature using a goniometer (NRL, Rame-Hart Instrument Co, Succasunna, USA) which was coupled to an automated pipetting system and analyzed using the DROP image advanced software. For each type of CL, six measurements were taken and the average values were considered. Contact angle hysteresis was also calculated using Eq. 3:

Contact Angle Hysteresis (°) = C_a— C_{r .} Eq. 3 where C_a and C_r are the advancing and receding contact angles respectively.

[0086] Atomic Force Microscopy

[0087] Surface roughness of the CLs was assessed using an atomic force microscopy (AFM; Innova, Bruker UK Limited, Coventry, UK). Four slits were made at the circumference of each CL before mounting onto a glass slide. The concave side of the CL was scanned in Tapping Mode across a scan area of 20 pm x 20 pm with a silicon cantilever with tip radius of approximately 8 nm. For each CL, three different locations were scanned. The images were then analyzed with NanoScope Analysis software (Version 1.10) and the roughness of the CL was presented as root mean square roughness (R_q).

[0088] Optical Transmittance

[0089] The spectral transmittances of coated and uncoated lenses were measured using a calibrated spectroradiometer (ILT950, International Light Technologies, Peabody, USA). Lenses were placed between two thin glass cover slips on top of the spectroradiometer sensor to perform the measurements. A standard LED light (3900K) was used as the light source for this procedure.

[0090] Field Emission Scanning Electron Microscopy

[0091] To determine the microbial adhesion and biofilm formation on the uncoated and coated contact lenses, MRSA DM9808R, S. aureus DM4400R and P. aeruginosa ATCC 9027 were first cultivated for 18 hours to reach their mid logarithmic growth phase in Tryptic Soy broth (TSB) at 37 °C in a shaking incubator. The initial bacterial concentration was adjusted by obtaining an optical density (OD) reading of 0.07 at 600 nm wavelength, which corresponds to concentration of McFarland 1 solution (3 x 10 CFU/mL), before the microbe solutions were further diluted to achieve a final inoculum of 3 x 10 CFU/mL on the CLs. 100 pL of this bacterial inoculum was then added dropwise to the uncoated and coated CLs in 24-well plates, and incubated at 37 °C. At day 1 and day post inoculation, a set of CLs were taken out, rinsed three times with sterile phosphate buffered serum (PBS) and examined for microbial adhesion or biofilm formation using field emission scanning electron microscopy (FESEM) and LIVE/DEAD backlight bacterial viability assay. For SEM analysis, CLs with the adhered microbes were first fixed using a solution mixture of 3% paraformaldehyde and 1.5% glutaraldehyde for an hour at room temperature. The dehydration of the CLs was then performed using 50, 70, 80, 90, and 100% ethanol for 10 minutes each. Finally the lenses were dried in hexamethyl disilane (HMDS) for 30 seconds followed by 10 minutes air-drying at room temperature. After mounting, a few nanometer thick conductive platinum film was coated on the CLs by sputter coating before imaging with FE-SEM (FEI-QUANTA 200F, the Netherlands).

[0092] Confocal Microscopy

[0093] To visualize the viable microbes and to estimate the bacterial average area coverage on the uncoated and coated CLs, a LIVE/DEAD Backlight bacterial viability kit (L- 7012, Invitrogen) with two staining agents (Propidium iodide and SYTO 9) was used. Propidium iodide is a red nucleic acid staining agent that labels dead bacterial cells by penetrating damaged cell membrane whereas SYTO 9 is a green fluorescent nucleic acid staining agent which label both live and dead microbes by penetrating the cells through the intact or damaged membrane. For staining, the CLs incubated in the bacterial culture were first removed, washed three times with PBS and then soaked in a dye solution (5.01 mM of SYTO 9 and 30 pM of propidium iodide in PBS) at room temperature in the dark for 15 min. The stained microbes on the contact lenses were then observed using oil immersed lOx or 63x objective lens of a Zeiss LSM 5 DUO laser scanning confocal microscope (Germany). Confocal images were then analyzed using IMARIS software and the total area coverage for different bacterial strains was estimated using ImageJ software. [0094] Corneal Thickness Measurements

[0095] For inserting the contact lenses, the nictitating membrane was removed from the rabbits' eyes. 1 week post removal, the rabbit eyes were examined by silt-lamp photography (FS-3V Zoom Photo Slit Lamp, Nickon, Tokyo) and AS-OCT (RTvue, Optovue, Fremont, CA) for corneal thickness measurements to ascertain there were any corneal aberrations, such as vascularization or other ocular defects. Uncoated and coated contact lenses were applied to the eyes and changed every 24 hours post insertions continuously for 5 days. Before removal of the contact lenses, similar measurements were made from day 1 to day 5 and at the end of the study.

[0096] Statistical analysis

[0097] The results were analyzed by t-test or l-way ANOVA using GraphPad Prism software and the data is presented as mean ± standard deviation. Equal variance was assumed and a p value of < 0.05 was considered statistically significant.

[0098] EXAMPLE 3: Preparation of B4010 and yMG incorporated pDA coated CLs

[0099] Designing a substrate-independent pDA coating using dopamine solution in Tris- HC1 (2% w/v dopamine, pH approximately 8.5) is a well-explored and established protocol. However, recent studies have revealed that a significant amount of Tris is undesirably incorporated into the pDA coatings when the traditional method of manufacture is used. In the present work, the aim was to design an antimicrobial bAMP/yMG glued-pDA coating for contact lens applications. Tris incorporation would be undesirable due to the possibility of it causing eye irritation and interference with bAMP/yMG immobilization. Therefore, the feasibility of replacing Tris with the biocompatible NaHC0₃ buffer (pH = 8.5) for dopamine polymerization was investigated.

[00100] A one-pot coating method wherein dopamine and the antimicrobials were deposited simultaneously from a single solution was used to minimize the number of coating steps. In a typical experiment, the contact lens was immersed in dopamine dissolved in sodium bicarbonate buffer (pH approximately 8.5) and the antimicrobial component such as B4010

bAMP or yMangostin (yMG; ) (dissolved in the same buffer) was added to generate antimicrobial nanocoatings. UV spectral studies indicated the formation of the pDA heterocyclic structure within 2 hours in the presence NaHC0₃ buffer and at a faster rate than in Tris-HCl. It is thought that the dopamine and B4010 bAMP together may undergo a Michael-type addition or Schiff-base formation to covalently bond to the surface of the CL, while dopamine may facilitate non-covalent bonding of yMangostin (yMG) on the CL surface via hydrogen bonding or p-stacking interactions (Fig. 9). To avoid excessive coloration of the CLs due to thick pDA coating and to combat its interference with peptide immobilization, coating on the CLs were carried out using NaHC0₃ buffer at lower concentration of dopamine (0.25% w/v dopamine, pH approximately 8.5 at 37 °C) for 2 hours with orbital shaking at 300 rpm.

[00101] A simplified flow diagram depicting the method of manufacture of the device is shown in Fig. 10, whereby the core material (1001) is contacted (1003) with a catecholamine compound, antimicrobial peptide and/or antimicrobial polymer and a biocompatible buffer (102). The coated core material (1004) is treated to remove the excess catecholamine compound, antimicrobial peptide and/or antimicrobial polymer and biocompatible buffer (1005), to form the biocompatible ophthalmic device (1006).

[00102] The presence of bAMP, a cationic peptide, was found to accelerate the pDA polymerization as indicated by the appearance of weak brown coloration on the lenses. However, for yMG, a 24 hour coating was required to obtain optimum attachment under similar conditions. After the coating, the clarity of the CLs and the wearer’s perception of colors through the CLs were assessed and compared with UCL. Fig. 1 compares the optical transparency of UCL and pDA coated contact lenses prepared under various conditions. Both bAMP-pDA-CL and yMG-pDA-CL displayed no loss of transparency when compared to UCL. Although the coatings affected the wearer’s ability to see white color, it did not affect the CL’s clarity and the wearer’s perception of other colors (Fig. 1). These results suggest that the coatings had minimal impact on the CL optical properties or their functional properties.

[00103] EXAMPLE 4: XPS characterization of pDA coated CLs

[00104] XPS measurements were performed to ascertain the changes in the surface chemistry after pDA coating and functionalization by the antimicrobials. Fig. 2A-C shows the high resolution XPS Cls, Nls and Ols core-level spectra of various samples. At a first glance, these spectra indicate substantial changes in the surface chemistry of the coated lenses when compared to uncoated CLs. The core-level spectra indicates that the shape and peak positions of Cls, Nls and Ols spectra were altered by various coating conditions. No nitrogen Nls peak was observed in uncoated contact lens which is in agreement with its composition. The Ols spectra showed substantial broadening, as indicated by the increase in Full width at half maximum (FWHM) of Ols spectra in the CLs after coating. This is attributed to the presence of multiple bonding states of C with O, consistent with the chemical structure of pDA, bAMP and yMG in coated CLs as compared to uncoated contact lens.

[00105] To obtain better insight into the types of chemical bonding present in various types of coatings, the deconvolution of Cls and Nls core level spectra was performed and are shown in Fig. 2D-G (C ls) and Fig. 2H-J (N ls). The deconvolution of Cls spectra revealed the presence of three peaks, namely , C₂ and C₃ at about 284.5, 285.9 and 288.4 eV which are assigned to C-C/C-H, C-N/C-0 and C=0/N-C=0 bonding, respectively. Similarly, the deconvolution of Nls spectra revealed the presence of three peaks, namely Ni, N₂ and N₃ positioned at 401, 399.5 and 398.6 eV which correspond to RNH₂ , R₂NH and =N-R bonding, respectively. Compared to uncoated contact lenses, the appearance of Nls spectra with its constituent peaks corresponding to RNH₂, R₂NH and =N-R bonding suggest the presence of pDA coating in all coated contact lenses. Moreover, the increase of C=0/N-C=0 (C₃ peak) bonding in all coated lenses compared to UCL further shows that the pDA coats the entire contact lens.

[00106] Next, the area under the Nls curves for all four samples were compared to determine the relative change in nitrogen in the designed contact lenses (Fig. 2K). It is evident from Fig. 2K that the application of pDA coating induces about a 3.7-fold enhancement in nitrogen with respect to UCL which further increases to about 4-fold in bAMP -pDA-CL, this being attributed to the polyamide structure of bAMP. Without being bound to theory, it appears that the pDA has a stronger affinity to the UCL, enabling the pDA to coat the CL. It also appears that bAMP is covalently anchored onto the pDA rather than to the CL itself.

[00107] EXAMPLE 5: Surface wettability analysis of CLs

[00108] The wettability of antimicrobial-pDA-coated contact lenses was evaluated by static contact angle measurements. A pristine, uncoated etafilcon A contact lens was found to have a contact angle ( 0_static) of 66.6 ± 3.5°, indicating the hydrophilic nature of the lens surface (Table 3). Upon pDA coating, 0_static increased to 73.2+3.1°, suggesting a slight decrease in the wettability after pDA coating. Simultaneous functionalization of CLs with pDA and antimicrobials, did not alter 0_static significantly (p>0.05), with the observed values of 75.6+1.5° and 72.8+4.3° for bAMP-pDA-CL and yMG-pDA-CL, respectively. When a contact lens is on the ocular surface, mechanical opening and closing of the eye lids will wet the lens surface and form pre-lens (prLTF) or post-lens tear films. The ability of PrLTF to reestablish itself during eye lid closure is an important parameter and indicates the stability of PrLTF on the CL. Therefore, contact angle hysteresis i.e., the difference in contact angle formed by expanding (advancing) or contracting (receding) the liquid was determined. CLs with small hysteresis are preferred as they are less likely to dehydrate and their wettability is less affected by the environment. The results indicated that pDA or antimicrobial-pDA- coating decreased the hysteresis values of uncoated CLs by approximately 1.5 times, suggesting that a stable PrLFT could be reestablished during eye lid closure on the bAMP- pDA-CL and yMG-pDA-CL (Table 3). Thus, it is likely that pDA and antimicrobial coating may improve in establishing PrLTF by decreasing the aqueous wettability.

[00109] Table 3. Surface wettability of antimicrobial-coated contact lenses.

Contact A ngles (^¾)

Type of CLs _

Static Advancing Receding Hysteresis

Bare CL 66.6 ± 3.5 92.3 ± 3.7 27.6 ± 7.2 64.7 + 3.5 pDA-coated CL 73.2 ± 3.1 92.1 + 1,6 49.1 ± 5.5 43.1 ± 3.9

Amp_pDA-coated CL 75.6 ± 1.5 90.9 + 1 5 50.9 ± 2.6 40.0 ± 1.1 yMG_pD A-coated CL 72.8 + 4.3 86.5 + 1.0 45.6 + 7.7 40.9 + 8.8

[00110] EXAMPLE 6: Surface roughness analysis of different CLs

[00111] Surface roughness of the CL affects the comfort of wear and its susceptibility to microbial colonization and protein adhesion. Hence, the effects of the coatings on the surface roughness of the CL were examined. AFM scanning revealed a homogeneous topography with a surface roughness of 1 nm for UCL (Fig. 3A). An insignificant increase in the surface roughness (R_q = 1.4 nm) was observed after pDA was coated using the NaHC0₃ method of synthesis compared to the traditional Tris-HCl method (Fig. 3B). This may be due to employing very low concentrations of dopamine (0.25% w/v) for the development of pDA coating which is less likely to form agglomerates that could adhere to CL surface and affect its surface roughness. However, formation of antimicrobial -pDA-coating increased the surface roughness of the CLs moderately with the estimated R_q values of 5 and 6.3 nm for bAMP-pDA-CL and yMG-pDA-CL respectively (Fig. 3C and 3D). Overall, the results indicate that the attachment of antimicrobials to the lens surface results in minimum variation in their optical properties, desirable decrease in the hysteresis and a moderate increase in their surface roughness.

[00112] EXAMPLE 7: Antimicrobial Properties and durability of coated CLs

[00113] Next, the antimicrobial properties of contact lenses coated with various antimicrobials were tested against S. aureus, MRS A and P. aeruginosa strains. The bacterial inoculum was exposed to uncoated and coated CLs for 24 hours and the amount of bacteria that survived in solution was determined. Uncoated CLs did not show significant reduction in the bacterial burden except for the MRSA DM21455 strain (Fig. 4a). However, exposure of all investigated Gram-positive strains to bAMP-pDA-CL resulted in a marked decrease in their viability, as indicated by a significant decrease in bacterial viability and higher R_f values (2 to >5) (Fig. 4A and Table 4). However, for Gram-negative P. aeruginosa strains, a moderate decrease (R_f = 0.8- 1.2 when compared to UCL) was observed for bAMP-pDA-CL (Fig. 4B and Table 4). Similarly, yMG-pDA-CL decreased the viability of S. aureus and MRSA substantially and no activity was observed against P. aeruginosa strains, consistent with our previous observations that yMG lacked antimicrobial activity against Gram-negative pathogens. Leaching studies revealed that despite showing continuous reduction in their antimicrobial activity, bAMP-pDA-CL could still reduce the growth of MRSA DM21455 by 2.52 log CFU and P. aeruginosa by 0.78 log CFU after 14 days (Fig. 4C and 4D). CLs coated with yMG-pDA-CL could also decrease the growth of MRSA by 1.06 log CFU. These results suggest that these coated CLs could prevent bacterial colonization for up to 14 days. [00114] Table 4. Reduction factor (R_f) determined from bacterial viability assay for uncoated and antimicrobials coated CLs.

a The values in the brackets represents percentage lethality (P) values estimated from the log reduction

(L) values using the equation P = (1-10^L) x 100

[00115] EXAMPLE 8: B4010-coated contact lenses inhibit S. aureus, MRSA and P. aeruginosa biofilm formation

[00116] Live/dead cell staining followed by confocal imaging was used to determine the efficacy of uncoated and coated CLs in preventing the microbial biofilm formation. Adhesion of S. aureus, MRSA and P. aeruginosa to the antimicrobial-coated CLs were examined by confocal microscopy and scanning electron microscopy. Confocal images of S. aureus and MRSA exposed to uncoated and coated contact lenses after day 1 and day 3 are shown in Fig. 5. Significant populations of both S. aureus and MRSA strains in the form of aggregates covered the entire area of uncoated and pDA-CL, and the effect was remarkable in the case of MRSA strains. However, fewer individual colonies of S. aureus and MRSA were visible on the surface of both bAMP-pDA-CL and yMG-pDA-CL coated CLs at day 1 and 3. These results indicate complete inhibition of S. aureus and MRSA biofilm formation by the antimicrobial-coated CLs.

[00117] Consistent with the confocal results, SEM results also indicated significant presence of S. aureus! MRSA cell aggregates wrapped in a dense exopolysaccharide matrix on uncoated as well as on pDA-coated contact lenses (Fig. 6 and 7). However, only fewer planktonic cells were observed on the antimicrobial coated contact lenses after day 1 and day

3. [00118] A similar effect was observed for bAMP-pDA-CL against P. aeruginosa strains. P. aeruginosa is the leading major etiological agent for contact lens-related microbial keratitis. Thus, the anti-biofilm properties of bAMP-coated lenses was confirmed as was determined for the S.aureus/MRSA strains. Both confocal and SEM images indicated the presence dense colonies of P. aeruginosa on UCL and pDA-CL surfaces at day 3 (Fig. 7). However, the images confirmed the presence of few planktonic bacterial cells on bAMP-pDA-CL surfaces. The adhered cells displayed considerable shrinkage and loss of membrane integrity, indicating that the antimicrobial-coated CLs retained the membranolytic action.

[00119] These results indicate that the antimicrobial-coated lenses displayed contact- mediated bactericidal activity, thus abrogating the adhesion and biofilm formation of pathogenic bacteria. Peptide immobilization by covalent bonding improved the antimicrobial activity for an extended period of time.

[00120] EXAMPLE 9: Biocompatibility of the Coated Contact Lenses

[00121] On the eye surface, CLs are always in contact with the epithelial cells. And if there are any breaches in the epithelium, the contents of the CLs may access the stromal cells. Hence, the cytocompatibility of the CLs towards telomerase-immortalized human comeal epithelial (hTCEpi) and human primary corneal stromal fibroblasts (hCSLb) cells was assessed. Since yMG and bAMP are known to kill bacteria by permeabilizing the bacterial cytoplasmic membrane, the cytotoxicity of these coatings was assessed using a LDH membrane integrity assay. As shown in Fig. 8, pDA-CL and bAMP-pDA-CL showed normal cellular morphology of hTCEpi and hCSLb cells. However, reduction in the cell size and lysed cellular structures were observed in case of yMG-pDA-CL. Consistent with these results, LDH assay also revealed insignificant reduction in hCSLb cells with pDA-CL (3%) and bAMP-pDA-CL (10%). Similarly, 0.5% and 23% cellular toxicity was observed for pDA-CL and bAMP-pDA-CL, respectively against hTCEpi cells. Among all the coated CLs, yMG-pDA-CL lenses showed significant cell toxicity of about 38% and 58% for hCSLb and hTCEpi cells, respectively. Thus, overall, pDA-CL and bAMP-pDA-CL were found to be biocompatible whereas yMG-pDA-CL showed cytotoxicity to both the investigated ocular cell lines.

[00122] EXAMPLE 10: Optimization of antimicrobial concentration

[00123] The cationic polymer e-poly-L-lysine (ePL) displays broad spectrum antimicrobial properties including multi-drug resistant Pseudomonas aeruginosa, Carbapenem-resistant Enterobacter (CREs), Candida spp., and Fusarium solani strains. The polymer is non- cytotoxic to ocular surface cells as well as a number of mammalian cells/cell lines. As the polymer is approved by the US FDA as a food preservative, use of the polymer would decrease the regulatory risks associated with the ocular device. Table 5 shows the ratio of dopamine:ePL for the preparation of antimicrobial contact lenses. Based on these studies, it was concluded that the conditions used for CL4 had optimum optical properties (Fig. 12), broad spectrum antimicrobial properties (Fig. 13A) and biocompatibility for human conjunctival epithelial cells and human cornea stromal fibroblasts (Fig. 13B and 13C).

[00124] Table 5. Preparation conditions and properties of the antimicrobial coated contact lenses

[00125] EXAMPLE 11: Antimicrobial durability of contact lens (CL4)

[00126] The durability of the antimicrobial coating was investigated as described above in Example 7.The results are expressed in terms of logio reduction in the viability of S. aureus 29213 and P. aeruginosa 9027 bacterial strains (Fig. 14). ePL-coated lenses retained the antimicrobial activity against both the bacterial strains even after 45 days of immersion in PBS, establishing excellent durability of the antimicrobial coating.

[00127] EXAMPLE 12: In vivo biocompatibility of contact lens

[00128] The biocompatibility of the lenses (CL0 and CL4) were determined by changing the lenses every day for 5 days and assessing the changes in the cornea by a slit lamp (SL) biomicroscopy, monitoring the changes in intraocular pressure and corneal thickness (by anterior-segment optical coherence tomography). SL images show that eyes inserted with CL0 or CL4 did not have any signs of corneal oedema, perforation or neovascularization after continuous application of the lenses for 6 days (changed 5 times). The individual values from each eye (n=4 per group) are shown in Fig. 15A and B. Intraocular pressure (IOP) measurements and central comeal thickness remained identical for both lens inserted eyes and no significant difference was determined (Fig. 16A-C). Taken together, these results demonstrate excellent biocompatibility of the CL4.

INDUSTRIAL APPLICABILITY

[00129] The biocompatible ophthalmic device is useful in preventing, suppressing or treating bacterial infection in an eye of a subject, in particular bacterial infection of the cornea. The device may facilitate facile prevention, suppression or treatment of an ophthalmic infection by allowing the user to simply wear the device. Additionally, the method of manufacturing a biocompatible ophthalmic device and the kit for preparing a biocompatible ophthalmic device are useful in facile preparation of the biocompatible ophthalmic device, whereby the ophthalmic device may be prepared without compromising the clarity or the colour perception when worn by the user. [00130] It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

SEQUENCES

Table 6: Linear sequences

Table 7: Branched sequences

Claims

1. A biocompatible ophthalmic device comprising:

a core material;

- a first component which is coating the surface of the core material; and

a second component which is linked to the first component by a bond; wherein

the first component comprises cross-links of at least one catecholamine compound and

- the second component comprises at least one antimicrobial peptide and/or at least one antimicrobial polymer.

2. The device according to claim 1, wherein the bond is a covalent bond or non-covalent bond.

3. The device according to any one of the preceding claims, wherein the catecholamine compound is selected from the group consisting of

The device according to any one of the preceding claims, wherein the catecholamine compound is dopamine (4-(2-aminoethyl)benzene-l,2-diol; 3,4-

dihydroxyphenethylamine;

norepinephrine (4-[(lR)-

2-amino- l-hydroxyethyl] benzene- 1 ,2-diol; Noradrenaline;

The device according to any one of the preceding claims, wherein the ophthalmic device is selected from the group consisting of optical prosthetic device, intraocular lens, artificial eye, contact lens, bandage contact lens, device care box, and ophthalmic surgical device.

The device according to any one of the preceding claims, wherein the ophthalmic device is selected from the group consisting of a contact lens, a bandage contact lens, and an intraocular lens.

7. The device according to any one of claims 1 to 5, wherein the core material is selected from the group consisting of hydrogel, poly(HEMA) hydrogels, silicone hydrogel, metals, sapphire (Al₂0₃), quartz, stainless steel, NiTi, Silicon, polymer, Acrylate/Methacylate Copolymer, glass, and silicon nitride. 8. The device according to any one of the preceding claims, wherein the core material is a hydrogel.

9. The device according to any one of the preceding claims, wherein the hydrogel is selected from the group consisting bufilcon A, epsifilcon A, etafilcon A, focofilcon A, methafilcon A, methafilcon B, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ocufilcon F, perfilcon A, phemfilcon A, tetrafilcon B, and vifilcon A.

10. The device according to any one of the preceding claims, wherein the hydrogel is etafilcon A.

11. The device according to any one of the preceding claims, wherein the antimicrobial peptide is selected from the group consisting of a peptide comprising at least one lysine residue (amino group), a peptide comprising at least one cysteine residue (thiol group), or a peptide comprising at least one histidine residue (imidazole group).

12. The device according to any one of the preceding claims, wherein the antimicrobial peptide comprising at least one lysine residue is selected from the group consisting of RGRKVVRRKK (SEQ ID NO. 1) (monomer),

RGRKVVRRKKRRVVKRGR (SEQ ID NO. 2) (linear retrodimer),

(RGRKVVRR)₂KKKi (bAMP B2088),

[(RGRKVVRR)₂K]₂KKi(bAMP B4010),

[(AGRKVVRR)₂K]₂KKi,

[(RARKVVRR)₂K]₂KKi,

[(RGAKVVRR)₂K]₂KKi,

[(RGRA VVRR)₂K] ₂KK_I,

[(RGRKA VRR)₂K] ₂KK_I,

[(RGRKVARR)₂K]₂KK_I,

[(RGRKVV AR)₂K] ₂KK_I,

[(RGRKVVRA)₂K]₂KKi;

[(RGAA VVRR)₂K] ₂KK_I,

[(RGRKVV AA)₂K] ₂KK_I,

[(RGAKA VRR)₂K] ₂KK_I, [(RGRKAARR)₂K]₂KKI,

[(RGAAAVRR)₂K]₂KKi,

[(RGAKAARR)₂K]₂KKI,

[(RGRAAARR)₂K]₂KKI,

[(RGAAAARR)₂K]₂KKI,

[(RGRKAAAA)₂K]₂KKI;

[(GRKVVRR)₂K]₂KKi,

[(RKVVRR)₂K]₂KK₁,

[(KVVRR)₂K]₂KKi,

[(VVRR)₂K]₂KKi,

[(VRR)₂K]₂KKi,

[(RR)₂K]₂KK_i

[(R)₂K]₂KK_i;

[(VRGRVRKR)₂K]₂KKi (scrambled bAMP B4010),

wherein i = 0 or 1.

13. The device according to any one of the preceding claims, wherein the antimicrobial peptide comprising at least one lysine residue is [(RGRKVVRR)₂K]₂KK (SEQ ID

NO.: 56) (

, bAMP B4010).

14. The device according to any one of the preceding claims, wherein the antimicrobial polymer is a polymer comprising at least one amino group, a polymer comprising at least one thiol group, a polymer comprising at least one imidazole group.

15. The device according to any one of the preceding claims, wherein the antimicrobial polymer comprising at least one amino group is selected from the group consisting of Poly-L- Lysine, Poly-D-Lysine, e-poly-L- Lysine, linear Polyethylenimine (linear PEI), and branched Polyethylenimine (branched PEI).

16. The device according to any one of the preceding claims, wherein the first component and the second component reduces the viability of a bacterium or a fungus.

17. The device according to any one of the preceding claims, wherein the first component and the second component prevents the adhesion of a bacterium or a fungus to said device.

18. The device according to any one of the preceding claims, wherein the bacterium is selected from the group consisting of Pseudomonas spp., Staphylococcus spp., and Serratia spp.

19. The device according to any one of the preceding claims, wherein the bacterium is selected from the group consisting of MRSA (Methicillin-resistant Staphylococcus aureus ), Staphylococcus aureus, and Pseudomonas aeruginosa.

20. The device according to any one of the preceding claims, wherein the fungus is selected from the group consisting of Fusarium spp.

21. A method of preventing, suppressing and/or treating ophthalmic infection in the eye of a subject comprising the placement of a device according to any one of claims 1 to 20.

22. A device according to any one of claims 1 to 20 for use in preventing, suppressing and/or treating ophthalmic infection in a subject.

23. The method according to claim 21, or the device according to claim 22, wherein the ophthalmic infection is selected from the group consisting of blepharitis, microbial keratitis, dacryocystitis, and orbital cellulitis. 24. The method according to claim 21, ot the device according to claim 22, wherein the ophthalmic infection is microbial keratitis.

25. A method of manufacturing a biocompatible ophthalmic device according to any one of claims 1 to 20, wherein the method comprises

contacting a core material with a mixture comprising at least one catecholamine compound, at least one antimicrobial peptide and/or at least one antimicrobial polymer, and a biocompatible buffer to allow the formation of a coat on the surface of the core material;

and

removing excess first component, second component, and biocompatible buffer.

26. The method according to claim 25, wherein the biocompatible buffer is an inorganic buffer.

27. The method according to claim 25 or 26, wherein the inorganic buffer is selected from the group consisting of, phosphate buffer, carbonate buffer (sodium bicarbonate or NaHC0₃ buffer), and ammonium bicarbonate buffer (or (NH₄)HC0₃).

28. The method according to any one of claims 25 to 27, wherein the inorganic buffer is carbonate buffer (sodium bicarbonate or NaHC0₃ buffer).

29. The method according to any one of claims 25 to 28, wherein the concentration of the catecholamine compound in the mixture is from 0.1 mg/mL to 0.5 mg/mL.

30. The method according to any one of claims 25 to 29, wherein the concentration of the catecholamine compound in the mixture is about 0.25 mg/mL.

31. The method according to any one of claims 25 to 30, wherein ratio of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture is from 1:1 to 1:10. 32. The method according to any one of claims 25 to 31, wherein ratio of the concentration of the catecholamine compound to the concentration of antimicrobial peptide and/or antimicrobial polymer in the mixture is about 1:2 or 1:8. 33. A kit for preparing a biocompatible ophthalmic device according on any one of claims

1 to 20, the kit comprising:

a core material; and

a mixture comprising:

a first component comprising at least one catecholamine compound;

a second component comprising at least one antimicrobial peptide and/or at least one antimicrobial polymer; and

a biocompatible buffer.