WO2009021286A1 - Nanoparticules encapsulées par organosilice - Google Patents

Nanoparticules encapsulées par organosilice Download PDF

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Publication number
WO2009021286A1
WO2009021286A1 PCT/AU2008/001174 AU2008001174W WO2009021286A1 WO 2009021286 A1 WO2009021286 A1 WO 2009021286A1 AU 2008001174 W AU2008001174 W AU 2008001174W WO 2009021286 A1 WO2009021286 A1 WO 2009021286A1
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Prior art keywords
nanoparticles
organosilica
hollow
encapsulated
active nanoparticles
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PCT/AU2008/001174
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English (en)
Inventor
Shizhang Qiao
Gao Qing Lu
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The University Of Queensland
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Priority claimed from AU2007904339A external-priority patent/AU2007904339A0/en
Application filed by The University Of Queensland filed Critical The University Of Queensland
Publication of WO2009021286A1 publication Critical patent/WO2009021286A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5115—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5094—Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites

Definitions

  • the present invention relates to mesoporous silica hollow spheres, and more particularly to mesoporous silica hollow spheres encapsulating nanoparticles within and processes for generating same.
  • Periodic mesoporous organosilicas are a relatively new class of organic-inorganic polymers which are characterized by highly ordered pores presenting a large surface area. These materials also exhibit low cytotoxicity, tuneable pore size and are biodegradable. This makes them potentially useful in a wide range of applications.
  • siloxane groups of PMOs provide structural rigidity to the polymer while the organic bridging groups allow for functionality and derivatisation.
  • the object of the invention is to overcome or at least alleviate one or more of the above problems and to provide for a hollow mesoporous organosilica structure which is useful in encapsulating nanoparticles.
  • the invention resides in a process for generating a hollow mesoporous organosilica structure encapsulating one or more active nanoparticles including the steps of:
  • the hollow template vesicle formation is achieved by contacting the one or more active nanoparticles with a fluorocarbon surfactant.
  • the fluorocarbon surfactant is FC4.
  • the one or more active nanoparticles to be encapsulated are coated with a long-chain coating surfactant prior to hollow template vesicle formation.
  • the organosilica component is selected from the group consisting of 1 ,2-bis(trimethoxysilyl)ethane, methyltrimethoxysilane, tetraethoxysilane, 1 ,4-bis(triethoxysilyl)benzene or bis[3-
  • the organosilica component may comprise a functionalised organosilica component displaying a functional group selected from the group consisting of amino, cyano, double bond, aromatic, thio, hydroxy or carboxy.
  • the process may further include the step of removing surfactant from the hollow mesoporous organosilica structure encapsulating one or more active nanoparticles.
  • the one or more active nanoparticles are magnetic nanoparticles.
  • the FC4 is present in an aqueous solution at a concentration of between 1.0x10 "3 g/mL to 15.0x10 "3 g/mL before contacting the one or more active nanoparticles to be encapsulated.
  • the invention resides in a hollow mesoporous organosilica structure encapsulating one or more active nanoparticles.
  • the diameter of the hollow mesoporous organosilica structure is between 100 nm to 300 nm.
  • the organosilica component of the hollow mesoporous organosilica structure may form a shell having a thickness of between 5 nm to 100 nm.
  • the pores of the mesoporous organosilica may have a diameter of between 1.5 nm to 10 nm.
  • the one or more active nanoparticles are magnetite nanoparticles.
  • the encapsulated magnetite nanoparticles display a saturation magnetization value of between 1.5 emu/g to 40.0 emu/g.
  • the invention resides in a hollow mesoporous organosilica structure encapsulating one or more active nanoparticles generated by forming a hollow template vesicle around the one or more active nanoparticles and polymerising an organosilica component onto the hollow template vesicle to form a hollow mesoporous organosilica structure encapsulating the one or more active nanoparticles.
  • FIG 1 is a schematic outline of the synthetic route towards an active nanoparticle encapsulating PMO according to one embodiment of the present invention
  • FIG 2a, b and c are a series of transmission electron microscope (TEM) images of an encapsulating PMO according to one embodiment of the present invention
  • FIG 3 (a) is a scanning transmission electron microscope (STEM) image and (b) an energy dispersive X-ray spectroscopy (EDX) spectrum of an amino functionalised encapsulating PMO according to one embodiment of the present invention
  • FIG 4 shows the N 2 adsorption/desorption isotherms with an inset showing pore size distribution calculated from the adsorption branch, of an amino functionalised encapsulating PMO according to one embodiment of the present invention
  • FIG 5 shows X-ray diffraction (XRD) patterns at low angles of an encapsulating PMO (curve a), and an amino functionalised encapsulating PMO (curve b) according to one embodiment of the present invention
  • FIG 6 is a series of scanning electron microscope (SEM) images of an encapsulating PMO according to one embodiment of the present invention wherein 0.3 g (image a), 0.45 g (image b) and 0.75 g (image c) of FC4 were used in the synthesis;
  • FIG 7 shows the field-dependent magnetization curves at 300 K of an encapsulating PMO synthesised with 0.3 g of FC4 (inset), an encapsulating PMO synthesised with 1.0 g of FC4 and double the amount of Fe 3 ⁇ 4 nanoparticles as for the inset example (curve b) and an encapsulating PMO synthesised with 0.45 g of FC4 (curve a) according to one embodiment of the present invention; and FIG 8 is a TEM image of an encapsulating PMO according to one embodiment of the present invention synthesised with 1.0 g of FC4 and double the amount of Fe 3 O 4 nanoparticles as in the other examples.
  • the inventors have developed a method of creating hollow mesoporous organosilica structures encapsulating one or more active nanoparticles. These structures have a highly ordered porous structure and their size, shell wall thickness and the number of active nanoparticles encapsulated within are all controllable. They exhibit many desirable properties such as small particle size, low density, high surface area and large pore volume making them suitable for a range of applications.
  • active nanoparticles as used herein describes nanoparticles which display a useful property. When encapsulated in the hollow mesoporous organosilica structures, the property of the active nanoparticles can still be used or manipulated externally to produce a desired result. Some non-limiting examples of the kinds of useful properties which may be displayed by the active nanoparticles are that they are magnetic, radioactive or light emitting.
  • the term "hollow” as used herein describes a periodic mesoporous organosilica structure which has been formed around an FC4 generated template vesicle which encapsulated the nanoparticles.
  • FC4 vesicle When the surfactant is removed the space which was defined by the FC4 vesicle becomes one large cavity within, and defined by, the organosilica structure.
  • the cavity or hollow will be a substantial part of the overall size of the PMO rather than a mere incidental space.
  • Magnetic nanoparticles have many uses such as in targeted drug delivery, biological separation and cell sorting applications.
  • Light emitting nanoparticles are employed in bio-labelling and imaging techniques.
  • the active nanoparticles employed are magnetic, Fe 3 O 4 (magnetite), nanoparticles.
  • the active nanoparticles employed are magnetic, Fe 3 O 4 (magnetite), nanoparticles.
  • Other non-limiting examples of nanoparticles which can be encapsulated in the present PMOs are CdSe, lanthanide doped NaYF 4 with downconversion or upconversion fluorescence, zeolite nanocrystals and quantum dots.
  • the nanoparticles take the form of nanocrystals.
  • the method of the present invention is clearly also applicable to a wider range of nanoparticles which do not take the form of nanocrystals.
  • FIG 1 demonstrates the steps required to form the PMO hollow spheres with encapsulated active nanoparticles.
  • Fe 3 ⁇ 4 nanoparticles in chloroform are prepared by methods which are well known in the art e.g. starting from iron oleate or Fe(acac) 3 complexes.
  • the surfactant cetyltrimethylammonium bromide (CTAB) is then used to transfer the Fe 3 O 4 nanoparticles into an aqueous solution containing C 3 F 7 ⁇ (CFCF 3 CF 2 ⁇ ) 2 CFCF 3 CONH(CH 2 ) 3 N + (C 2 H 5 ) 2 CH 3 r (FC4), as set out in more detail in Example 1.
  • CTAB cetyltrimethylammonium bromide
  • FC4 is a fluorocarbon surfactant whose molecules can form vesicles in aqueous solution.
  • the Fe 3 O 4 nanoparticles stabilised with CTAB then become encapsulated into these vesicles while in a basic aqueous solution, as seen in part (c) of FIG 1.
  • the organosilica precursor, 1 ,2-bis(trimethoxysilyl)ethane (BTME), is then introduced and, after hydrolysis and condensation reactions, forms a coating around the FC4 template through a surfactant to inorganic species (S + I " ) attraction pathway as seen in part (d) of FIG 1.
  • the last step to generate the PMO structure then involves crystallisation to put down further layers of the organosilica component to give the encapsulating PMO structure shown in part (e) with the surfactants still present.
  • a subsequent step is then performed to remove the surfactant from the structure. This may be achieved in a number of ways which would be known to a person skilled in the art, such as refluxing in ethanol with or without HCI acid.
  • FC4 The critical step towards obtaining highly ordered hollow PMO structures encapsulating active nanoparticles is the template formation using FC4. While not wishing to be bound by any particular theory, it is the formation of template vesicles by FC4 which allows the encapsulation of the CTAB stabilised Fe 3 ⁇ 4 nanoparticles in the basic aqueous solution and acts as a 'seed' for the vesicle templating process resulting in the mesoporous shell structure being laid down.
  • FC4 and CTAB act as co-templates for the formation of the hollow sphere and mesoporous shell structures seen in FIG's 2 a, b and c.
  • the shell structures in FIG's 2 a and b can be seen to possess a highly ordered hexagonal mesostructure which was further confirmed by X-ray diffraction.
  • the FC4 spontaneously forms vesicle-like structures in aqueous solution which exhibit a high degree of flexibility.
  • a combination of vigorous stirring and strong interactions between the FC4 and the CTAB stabilised Fe 3 O 4 nanoparticles results in the CTAB stabilised Fe 3 ⁇ 4 nanoparticles becoming encapsulated within the FC4 vesicles.
  • the organosilica precursor may then interact with the hydrophobic group of FC4 and, under appropriate conditions, will hydrolyse and self- assemble into composite vesicles through a vesicle templating process. As mentioned previously, these vesicles may act as a 'seed' for further growth and a liquid crystal templating process produces the final mesoporous shell structure.
  • FC4 to form a hollow vesicle template
  • Any surfactant which is capable of achieving this encapsulating structure may be suitable for use in the present process and is considered within the scope of the invention.
  • Other fluorocarbon surfactants may be particularly suitable in this regard, for example, the surfactants CF 3 (CF 2 WEO) 10 , FSO- 100, CF 3 (CF 2 )S(EO) 14 or FSN-100 may all aid in template vesicle formation.
  • PMO structure for example, to enable interactions with drug molecules.
  • other suitably functionalised organosilicas can be introduced along with BTME in the condensation step or subsequently when growing the organosilica shell.
  • These functionalised organosilica components may, when incorporated, display useful functionalities such as amino, cyano, double bond, aromatic, thio, hydroxy, carboxy and groups and the like which can be used to attract or bind a variety of molecules.
  • Non-limiting examples of such functionalised organosilicas are 3-aminopropyltriethoxysilane (APTES), 4- triethoxysilyl-butyronitrile, vinyltriethoxysilane, phenyltrimethoxysilane and 3- mercaptopropylmethoxysilane.
  • APTES 3-aminopropyltriethoxysilane
  • 4- triethoxysilyl-butyronitrile vinyltriethoxysilane
  • phenyltrimethoxysilane phenyltrimethoxysilane
  • 3-mercaptopropylmethoxysilane 3-aminopropyltriethoxysilane
  • this additional component will still result in a highly ordered meso-structure, without damage to the shell structure, which is now capable of additional functions, such as drug delivery, by making use of the amino or other functional group.
  • the average size of the amino functionalised PMO structures as synthesised via the method of Example 1 is about 165 nm.
  • Example 1 The synthetic procedure is detailed in Example 1 but, as an outline, involves the addition of Fe 3 O 4 nanoparticles (with associated hydrophobic ligands) dispersed in chloroform to an aqueous solution containing CTAB. After vigorous stirring of the resulting solution, a homogeneous oil-in-water micro-emulsion was obtained. Heating at 60-70 0 C for 10 to 30 min resulted in evaporation of the chloroform thereby generating aqueous-phase dispersed nanoparticles.
  • this heating step is important in achieving an ordered mesostructure in the final PMO product.
  • the heating temperature and time may vary depending on the organic solvent the nanoparticles are initially dispersed in but should always be adequate to ensure substantially complete removal of said solvent before the next step of introducing the template vesicle forming surfactant.
  • the resulting ordered mesostructure made possible by this step has a knock on effect in terms of also being able to successfully achieve tuneable pore size and magnetisation values (when magnetic nanoparticles are employed).
  • FC4 was then dissolved in water and stirred at room temperature for 1 h before the addition of CTAB and NaOH (2 M).
  • the aqueous-phase dispersed Fe 3 O 4 nanoparticles were added into the system and the solution heated to 8O 0 C.
  • BTME and APTES (optional for functionalisation of the PMO) were introduced with vigorous stirring.
  • the product was collected by filtration and dried at room temperature. To remove the surfactant, the product samples were refluxed in ethanol.
  • FIG 3 shows a scanning transmission electron microscope (STEM) image of the structure and an energy dispersive X-ray spectroscopy (EDX) spectrum of the amino functionalised encapsulating PMO.
  • STEM scanning transmission electron microscope
  • EDX energy dispersive X-ray spectroscopy
  • Each PMO sphere contains several monodispersed magnetite nanoparticles which show up as the bright spots on the STEM image in FIG 3.
  • the EDX spectrum represents one of these bright spots and indicates the presence of Fe (from the magnetite nanoparticles), fluorine (from the FC4), N (from the amino functionality) in low quantities and carbon and silicon from the BTME.
  • Figure 4 shows the N 2 adsorption-desorption isotherms for the amino functionalised encapsulating PMO of Example 1.
  • the type IV isotherm with a remarkably sharp capillary condensation step between 0.2 and 0.4 P/P o indicates that the sample possesses a highly ordered mesoporous structure.
  • a type H4 loop with parallel branches at relative pressures between 0.45 and 1.0 is attributed to the hollow cavity space.
  • the pore size (2.9 nm) of the surfactant extracted amino functional sample is obtained by pore size distribution calculated by the BJH model, as shown on the inset of Figure 4.
  • the BET surface area and pore volume are 613 m 2 g "1 and 0.912cm 3 /g, respectively.
  • the pore size of the hollow mesoporous structure will depend on the particular long-chain carbon surfactant used. In one embodiment the pores will have a diameter of between 1.5 nm to 10 nm. In a preferred embodiment the pores will have a diameter of between 2.5 nm to 6 nm.
  • Figure 5 is a powder X-ray diffraction (XRD) pattern of a magnetite nanoparticle encapsulating PMO synthesised using 0.45 g of FC4 (curve a) and including the amino functionalisation (curve b). These show that the samples exhibit a highly ordered two dimensional mesostructure with the typical hexagonal pattern of P6m symmetry.
  • XRD powder X-ray diffraction
  • the relevant experiments were carried out as described in Example 1 but with the amount of FC4 used either lowered to 0.3 g (3.5x10 "3 g/mL solution of FC4 in water before addition of CTAB and nanoparticles) or elevated to 0.75 g (8.7x10 "3 g/mL solution of FC4 in water).
  • the results showed that increasing the amount of FC4 used from 0.3 g to 0.75 g produced PMO hollow spheres which had decreased in size from around 230 nm to 130 nm.
  • the diameter of the PMO hollow structures of the invention ranges between 100 nm to 300 nm. In a preferred embodiment the diameter ranges from between 120 nm to 250 nm. As discussed, the actual diameter achieved will depend upon the relative amount of FC4 used.
  • the organosilica shell also became thinner on increasing the amount of FC4 used from 0.3 g to 0.75 g, having been reduced from more than 75 nm thick to 15 nm, as detected by use of a transmission electron microscope (TEM).
  • TEM transmission electron microscope
  • the organosilica shell of the structures of the invention is between 5 nm to 100 nm thick. In a preferred embodiment the shell is between 10 nm to 80 nm thick.
  • FIG 6 is a series of SEM's showing the spherical PMO particles produced when using 0.3 g (a), 0.45 g (b) and 0.75 g (c) of FC4. An important result of this is the effect it has on the saturation magnetisation value of the magnetic nanoparticle containing structures.
  • the average size of these structures is about 170 nm and so the size has not continued to decrease when the amount of FC4 was increased from 0.75 g to 1.0 g, as was the case when increasing from 0.3 g to 0.75 g of FC4.
  • FC4 plays a crucial role not only in encapsulating the active nanoparticles but also in controlling the structural development of the PMO sphere.
  • this encapsulating PMO structure displayed a saturation magnetisation value of 31.0 emu/g, curve 'b' of FIG 7, and the advantages of such a high saturation magnetisation value have already been discussed.
  • the saturation magnetisation value of the PMOs can therefore be controlled which gives a crucial advantage in applications which take advantage of the magnetic properties of the encapsulated nanoparticles, such as targeted drug delivery under magnetic field control.
  • the saturation magnetisation value of the hollow mesoporous organosilica structures is between 1.5 emu/g to 40.0 emu/g. In a preferred embodiment the saturation magnetisation value is between 2.0 emu/g to 35.0 emu/g.
  • FC4 may be present in an aqueous solution at a concentration of between 1.0x10 " 3 g/ml to 15.0x10 "3 g/ml before addition to the one or more active nanoparticles to be encapsulated.
  • the FC4 is present in an aqueous solution at a concentration of between 3.0x10 "3 g/ml to 12.0x10 "3 g/ml before addition to the one or more active nanoparticles to be encapsulated.
  • This concentration range relates to the concentration of the FC4 solution upon being made up in water and before it is added to any further solutions or vice versa.
  • BTME has been described as the organosilica precursor herein
  • suitable alternatives would be tetraethoxysilane, 1,4- bis(triethoxysilyl)benzene (BTEB), methyltrimethoxysilane and bis[3- (trimethoxysilyl)propyl]amine (BTMPA) as well as the use of 3- aminopropyltriethoxysilane (APTES) and other functionalised organosilica components.
  • CTAB is employed in the first instance as a suitable surfactant to enable the transfer of the F ⁇ 3 ⁇ 4 nanoparticles into an aqueous solution. This is necessary because the starting material for the synthesis of the magnetite nanoparticles possesses hydrophobic ligands. Transfer into aqueous solution then allows template formation with FC4 to proceed. Any surfactant which can achieve this may be considered suitable for use in the present invention. The use and choice of a particular surfactant will clearly depend on the particular type of active nanoparticles being encapsulated and how difficult it is to get them into an aqueous solution.
  • CTAB or an equivalent may not be necessary and this transfer step is avoided.
  • CTAB or an equivalent surfactant also has an effect on the pore formation in the resulting PMO structure.
  • CTAB has a Ci 6 carbon chain and clearly if a similar surfactant is chosen with a greater or smaller carbon chain length, e.g. a C 2 o to C 10 CTAB analogue, then this will impact on the pore size achieved in the final structure.
  • surfactants of different chain lengths such as octadecyltrimethylammonium bromide, myristyltrimethylammonium bromide or even those of a different basic structure, such as cetylpyridinium bromide, will be useful and are within the scope of the present invention.
  • This degree of control over pore size is very important as different applications of the final PMO products will require differently sized molecules to be able to enter the pores e.g. in separation/purification applications.
  • active nanoparticles are envisaged as being encapsulated in the manner described. These active nanoparticles may be chosen for the particular properties they display, as with the magnetic property of the Fe 3 ⁇ 4 nanoparticles described herein.
  • Other useful active nanoparticles for encapsulation by the method described herein include, but are not limited to, CdSe, lanthanide doped NaYF 4 with downconversion or upconversion fluorescence, zeolite nanocrystals and quantum dots.
  • Example 2 sets out the procedure for loading and measuring the subsequent release of ibuprofen and aspirin, representing hydrophobic and hydrophilic drugs respectively, from the nanoparticle encapsulating hollow PMO structure containing the amino group as introduced by the addition of 3- aminopropyltriethoxysilane (APTES).
  • APTES 3- aminopropyltriethoxysilane
  • the presence of the encapsulated magnetic nanoparticles allows the hollow PMO carrier to be concentrated at a specific area of the patient's body using a magnetic field and so the release of the drug can be localised. This will be particularly important in treatments such as cancer therapy where the release of toxic drugs can be made more site specific and so the treatment is more effective and lower amounts of the drug may be used leading to a reduction in the severity of side effects.
  • FC4 templating method as described herein provides for PMOs with a hollow interior which can encapsulate a variety of nanoparticles. Having the nanoparticles held within this internal cavity provides distinct advantages over the prior art. For example, the nanoparticles are much less likely to block the pores of the PMO or damage the mesoporous structure when incorporated in this manner.
  • control over the amount and/or concentration of FC4 used provides a large degree of control over the properties of the resulting hollow PMO structure.
  • the size of the PMO, the thickness of the shell wall, the numbers of nanoparticles encapsulated and, importantly, the saturation magnetisation value (when using magnetic nanoparticles) can all be tuned to desired levels using the present method. This provides a greater level of control over the encapsulation process than prior art methods and may allow larger numbers of nanoparticles to be carried, thereby (in the case of magnetite) allowing higher saturation magnetisation values to be achieved. This results in many functional advantages being offered by use of the present method.
  • Example 1 0.5 mL of Fe 3 O 4 nanoparticles dispersed in chloroform (15 mg/mL) was added to 10 mL of an aqueous solution containing 0.2 g of CTAB. After vigorous stirring of the resulting solution, a homogeneous oil-in-water micro- emulsion was obtained. Heating at 60 0 C for 10 min resulted in evaporation of the chloroform thereby generating aqueous-phase dispersed nanoparticles. 0.45 g of FC4 was dissolved in 86 g of water (5.2x10 "3 g/mL final concentration) and stirred at room temperature for 1 h before the addition of 0.05 g of CTAB and 0.7 mL NaOH (2 M).
  • Example 1 10 mg of the product of Example 1 was added into 10 mL of 2 mg/mL ibuprofen solution in hexane or 10 mL of a 0.4 mg/mL aspirin aqueous solution, respectively.
  • the mixture was contained in a sealed vial and was dispersed by ultrasonication for 30 min and shaken at room temperature at
  • the particles loaded with the drugs were collected by a magnet, and the solution was washed off and the content of drugs in the PMO structures was analysed to obtain the loading amount of drugs in each sample.
  • the powder was dried in a vacuum oven overnight at 60 0 C.

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Abstract

L'invention porte sur un procédé pour générer une structure d'organosilice mésoporeuse, creuse, encapsulant une ou plusieurs nanoparticules actives. Le procédé consiste à former une vésicule matrice creuse autour d'une ou plusieurs nanoparticules actives; à polymériser un composant d'organosilice sur la matrice. Le procédé permet de contrôler la dimension de pore, l'épaisseur d'enveloppe et la dimension globale des structures. Les structures d'organosilice mésoporeuses creuses fournies permettent d'encapsuler des nanoparticules de magnétite à des taux qui présentent des valeurs de magnétisation élevées applicables dans des domaines tels que l'administration de médicament ciblé, la séparation biologique et le tri cellulaire.
PCT/AU2008/001174 2007-08-13 2008-08-12 Nanoparticules encapsulées par organosilice WO2009021286A1 (fr)

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WO2012001012A3 (fr) * 2010-06-28 2013-01-31 Centrum Für Angewandte Nanotechnologie (Can) Gmbh Combinaison micellaire comprenant une nanoparticule et une pluralité de ligands tensioactifs polymérisables (surfomères)
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CN104394853A (zh) * 2012-02-19 2015-03-04 纳维基因股份有限公司 多孔性纳米结构在递送中的用途
CN104900364A (zh) * 2015-05-07 2015-09-09 梧州市产品质量检验所 超顺磁性Fe3O4/APTES复合纳米粒子及其制备方法
CN105036145A (zh) * 2015-07-20 2015-11-11 清华大学 一种一步法制备的有序介孔有机氧化硅空心球及其制备方法
CN109330989A (zh) * 2018-09-29 2019-02-15 西北大学 一种用于微波可控药物缓释的花状纳米载体及制备方法
CN109771666A (zh) * 2019-03-27 2019-05-21 南京邮电大学 一种柔性介孔有机硅纳米棒及其制备方法和应用
CN110479369A (zh) * 2019-08-20 2019-11-22 青岛科技大学 Yolk-shell型催化剂及其合成方法、以及其催化乙酰丙酸制备γ-戊内酯的方法
CN113134096A (zh) * 2021-03-19 2021-07-20 南方医科大学 一种兼具反向对比磁共振成像与药物控释功能的中空介孔有机硅复合纳米材料及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6027666A (en) * 1998-06-05 2000-02-22 The Governing Council Of The University Of Toronto Fast luminescent silicon
US20040180096A1 (en) * 2003-01-24 2004-09-16 Paras Prasad Ceramic based nanoparticles for entrapping therapeutic agents for photodynamic therapy and method of using same
US20050130167A1 (en) * 2002-10-25 2005-06-16 Gang Bao Multifunctional magnetic nanoparticle probes for intracellular molecular imaging and monitoring
US20060018966A1 (en) * 2003-07-22 2006-01-26 Lin Victor S Antimicrobial mesoporous silica nanoparticles

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6027666A (en) * 1998-06-05 2000-02-22 The Governing Council Of The University Of Toronto Fast luminescent silicon
US20050130167A1 (en) * 2002-10-25 2005-06-16 Gang Bao Multifunctional magnetic nanoparticle probes for intracellular molecular imaging and monitoring
US20040180096A1 (en) * 2003-01-24 2004-09-16 Paras Prasad Ceramic based nanoparticles for entrapping therapeutic agents for photodynamic therapy and method of using same
US20060018966A1 (en) * 2003-07-22 2006-01-26 Lin Victor S Antimicrobial mesoporous silica nanoparticles

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LING ZHANG ET AL.: "Magnetic Hollow Spheres of Periodic Mesoporous Organosilica and Fe304 Nanocrystals: Fabrication and Structure Control", ADVANCED MATERIALS, vol. 20, 29 January 2008 (2008-01-29), pages 805 - 809, XP055351656 *

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WO2012001012A3 (fr) * 2010-06-28 2013-01-31 Centrum Für Angewandte Nanotechnologie (Can) Gmbh Combinaison micellaire comprenant une nanoparticule et une pluralité de ligands tensioactifs polymérisables (surfomères)
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US9711266B2 (en) 2012-01-23 2017-07-18 Nvigen, Inc. Low density, highly porous nano structure
CN104394853B (zh) * 2012-02-19 2017-10-10 纳维基因股份有限公司 多孔性纳米结构在递送中的用途
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US10398905B2 (en) 2012-02-19 2019-09-03 Nvigen, Inc. Uses of porous nanostructure in delivery
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