CN113975249B - Preparation of Tris-BNP nano-particles and application thereof in treatment of skin diseases - Google Patents
Preparation of Tris-BNP nano-particles and application thereof in treatment of skin diseases Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
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- 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
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
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- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
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Abstract
The invention belongs to the technical field of drug carrier materials, and particularly relates to preparation of Tris-BNP nano-particles and application of the Tris-BNP nano-particles in treatment of skin diseases. The preparation method comprises the steps of preparing PLA and HPG into NNPs, carrying out redox reduction on the NNPs by using sodium periodate to obtain nano-particle BNPs with bioadhesion, and finally dispersing the BNPs in Tris-HCL to neutralize the bioadhesion of the nano-particle BNPs to obtain the Tris-BNPs nano-particles. The prepared Tris-BNPs can well penetrate through the stratum corneum of the skin and penetrate into the deep part of the skin when the stratum corneum of the skin becomes loose under a disease state (such as psoriasis), and the Tris on the Tris-BNPs can gradually diffuse along with the penetration of the Tris-BNPs into tissues, so that the BNPs can restore the biological viscosity, can be retained in the deep part of the skin, can be used as a carrier loaded with a medicament, is applied to the treatment of skin diseases and plays a better treatment effect.
Description
Technical Field
The invention belongs to the technical field of drug carrier materials, and particularly relates to preparation of Tris-BNP nano-particles and application of the Tris-BNP nano-particles in treatment of skin diseases.
Background
In the process of skin disease, symptoms such as pain and pruritus are often accompanied, the aesthetic degree is influenced, the physical health of a patient is influenced, and a heavy psychological burden such as psoriasis is brought to the patient.
Psoriasis, a common chronic and persistent skin disease which is easy to recur, is clinically manifested by chronic and noninfectious skin lesions with different degrees of severity, heavier psoriasis patients can affect 20% -80% of the whole body skin, the range of affected skin is wide, psoriasis with certain limited range (such as only affecting palmoplantar skin) is also of a serious type because of causing dysfunction, and the psoriasis can cause damage to patients in aspects of physiology and psychology no matter how large the range of skin lesions is. The primary purpose of psoriasis treatment is to remove skin lesions within a certain period of time, especially for severe psoriasis patients, and the treatment purpose is to relieve the clinical symptoms of the psoriasis patients, such as skin inflammation, redness, swelling, exfoliation, itching, pain, and the like, and prevent recurrence, thereby gradually achieving the purpose of healing.
The traditional drug delivery systems currently used for treating psoriasis are mainly divided into systemic delivery and local delivery. Among them, systemic delivery generally refers to an internal drug system, and is administered orally, but systemic administration by oral administration often causes problems of poor bioavailability due to first pass effect, fast clearance, poor skin deposition, and adverse reactions and interactions of drugs that limit and challenge their use and require careful monitoring. Topical delivery, referred to as topical drug systems, is the primary means of treating psoriasis, but topical therapy also suffers from a number of problems, such as difficulty in penetrating the stratum corneum with the larger particle size of the drug to allow the drug to reach the focal site; or the medicine can not stay in the focus part for a long time, and needs to be administered for many times; or the medicine has no tissue selectivity, so the medicine is easy to damage healthy skin tissues when being used externally; or the medicine texture is not waterproof and easily causes the focus part to be airtight, so the psoriasis treatment effect is always poor by a local medicine delivery mode (namely, the medicine is directly coated on the surface of the skin for transdermal administration).
Therefore, there is a need for a drug delivery system that overcomes the skin permeation barrier and delivers a specific amount of drug at a specific site for a long period of time, thereby improving therapeutic efficacy and reducing side effects.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a preparation method of Tris-BNP nano particles, and the prepared Tris-BNP nano particles can penetrate through the skin and permeate into the skin, can be detained in the deep position, release the medicament in a sustained and controlled manner, prolong the medicament dosage, achieve better treatment effect and can be applied to the treatment of skin diseases.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides a preparation method of Tris-BNP nano-particles, which comprises the following steps:
s1, PLA-HPG synthesis: dissolving PLA in DCM, dissolving HPG in DMF, combining the two solutions, drying, adding N, N' -diisopropylcarbodiimide and 4-dimethylaminopyridine, and reacting for 4-6 days at room temperature by stirring; after reaction, the product is prepared by precipitation;
s2, respectively preparing a PLA-HPG solution and a drug solution by using EA, then uniformly mixing the PLA-HPG solution, the drug solution, EA and DMSO, transferring the mixture into a certain amount of water, performing three times of ultrasonic treatment to obtain a small-volume nanoemulsion, transferring the small-volume nanoemulsion into the water in a stirring state again, evaporating the small-volume nanoemulsion until no bubbles are generated, and obtaining a crude product of the drug/NNPs, wherein the crude product is purified by an ultrafiltration tube to obtain the drug/NNPs;
s3, adding a sodium periodate solution into the medicines/NNPs to react for 2-30min; adding sodium sulfite solution to stop reaction, and purifying by an ultrafiltration tube to obtain bioadhesive nano-particle medicines/BNPs for treating skin diseases;
s4, properly diluting the drug/BNPs in the step S4 by using Tris-HCL to prepare Tris-BNPs nanoparticles.
Preferably, the concentration of Tris-HCL is 5mM.
Preferably, the drug/BNPs are diluted to a concentration of 1.0-2.0mg/mL using Tris-HCL. Specifically, drug/BNPs were diluted to a concentration of 1.5mg/mL using Tris-HCL.
Nanoparticles (BNPs) prepared based on PLA-HPG have excellent biocompatibility and bioadhesion. However, the surface of BNPs has abundant aldehyde groups, so that nanoparticles are stably retained on tissues through reaction with amino groups of the tissues, and Tris-BNPs developed by the bioadhesive nanoparticles based on PLA-HPG can well penetrate through the skin and deeply (but cannot penetrate through the complete stratum corneum of healthy skin) when the skin stratum corneum disease state (such as psoriasis) becomes loose, because the amino groups of Tris can react with the aldehyde groups of BNPs to temporarily block the bioadhesive property of BNPs, and in-vivo and in-vitro experiments also prove that Tris gradually leaves along with the penetration of BNPs into the tissues, so that the BNPs are finally recovered into the bioadhesive nanoparticles, thereby being capable of retaining in the deep skin, slowly and controllably releasing drugs, prolonging the drug dosage and the action time of the drugs, and further achieving better treatment effect, and being applied to the treatment of various skin diseases in a mode of encapsulating various skin disease drugs.
Preferably, the concentration of the PLA-HPG solution is 100mg/mL and the concentration of the drug solution is 50mg/mL.
Preferably, the volume ratio of the PLA-HPG solution, the drug solution, EA and DMSO is 0.225:0.050:0.225:0.350.
preferably, in step S3, the volume ratio of the mixed solution of PLA-HPG solution, drug solution, EA and DMSO to the water consumption for the first transfer and the second transfer is 0.85:2:10.
preferably, the concentration of the sodium periodate solution is 0.1mol/L, and the volume ratio of the sodium periodate solution to the drugs/NNPs is 1-3:1.
Preferably, the ultrafiltration tube purification in steps S3 and S4 is performed once by centrifugation, twice by washing with water, and repeated three times in total, each centrifugation being performed at 4 ℃, at 4500rpm, for 15min.
Preferably, the preparation method of HPG is: putting 1,1,1-trimethylolpropane in oil bath at 90-100 ℃ under inert gas atmosphere until completely dissolved, adding potassium methoxide, vacuumizing, refilling with inert gas after 10-30 minutes, then adding 25mL of glycidol within 12 and half hours to obtain crude HPG, and purifying the crude HPG to obtain HPG.
The invention also provides the Tris-BNP nano-particle prepared by the preparation method of the Tris-BNP nano-particle.
The invention also provides application of the Tris-BNP nano-particles in preparation of a medicament for treating skin diseases, wherein the medicament (namely the medicament in the medicament/BNPs) carried in the Tris-BNP nano-particles is a medicament for treating skin diseases.
Preferably, the skin disease is psoriasis.
Preferably, the drug for treating skin diseases is an external drug for treating skin diseases.
Further, the drugs for treating skin diseases include, but are not limited to, betamethasone dipropionate. Other drugs for treating skin-like diseases are also suitable for use in the present invention.
In addition, other drugs, even dyes (such as Cy 5), which can be entrapped in the Tris-BNP nanoparticles of the invention, are also suitable for use in the invention, whether these drugs are used for the treatment of skin diseases or other diseases treated by osmotic drugs.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a method for preparing Tris-BNP nanoparticles based on PLA-HPG bioadhesive nanoparticles, which comprises the steps of preparing PLA and HPG into NNPs, carrying out redox reduction on the NNPs by sodium periodate to obtain nanometer particle BNPs with bioadhesive properties, and finally dispersing the BNPs in Tris-HCL to neutralize the bioadhesive properties of the Tris-BNPs to obtain the Tris-BNPs nanoparticles. The prepared Tris-BNPs can not penetrate through the intact horny layer of healthy skin, but when the horny layer of the skin becomes loose under a disease state (such as psoriasis), the prepared Tris-BNPs can well penetrate through the horny layer of the skin and permeate into the deep part of the skin, and Tris on the Tris-BNPs can gradually diffuse along with the permeation of the Tris-BNPs into tissues and finally become BNPs to restore the biological viscosity, so that the Tris-BNPs can be bonded with proteins in the deep part of the skin and can be retained in the deep part of the skin. The prepared Tris-BNPs can be used as a carrier to load drugs, is applied to the treatment of skin diseases, and can exert better treatment effect.
Drawings
FIG. 1 is a graph of fluorescence profiles on dorsal skin longitudinal sections of psoriatic mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs);
FIG. 2 is a graph of fluorescence quantification on dorsal skin longitudinal sections of psoriatic mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs);
FIG. 3 is a graph of the fluorescence distribution of the dorsal skin of psoriasis mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs) at different time points;
FIG. 4 is a graph of fluorescence quantification of the dorsal skin of psoriatic mice at different time points after treatment with different nanoparticles (NNPs, BNPs, tris-BNPs);
FIG. 5 is a graph of the variation of the skin on the back of mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs) and applied with BD antigens;
FIG. 6 is a PASI score statistic of the skin on the back of mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs) and applied with BD antigens;
FIG. 7 shows the body weight of mice treated with different nanoparticles (NNPs, BNPs, tris-BNPs) and applied with BD antigens.
Detailed Description
The following further describes embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, and is not intended to limit the present invention. In addition, the technical features involved in the respective embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
Example 1 preparation of Tris-BNPs nanoparticles (entrapped dye Cy 5)
Preparing BNPs (cationic BNPs) entrapping dye by adopting an emulsion method:
(1) Synthesis of HPG (hyperbranched polyglycidyl ether):
4.67mmol 1, 1-Trimethylolpropane (TMP) was added to a 95 ℃ oil bath flask under argon protection, and after complete dissolution, 1.4mmol KOCH was added 3 (potassium methoxide), the flask was connected to a vacuum pump, and the flask was evacuated to a vacuum state and then refilled with argon after 10 minutesAnd the entire flask was filled all the way through, then 25mL of glycidol was added over 12 and a half hours by a microsyringe pump to give crude HPG. The crude HPG was dissolved in methanol and precipitated with acetone, and this procedure was repeated two or three times to purify the HPG; then dialyzing the HPG in ultra pure water through dialysis bags (500-1000D) to remove some HPG of small molecular weight, replacing the water every 5 hours; and finally, adding acetone to precipitate HPG again, and drying the HPG for 8-10h at 85 ℃ under vacuum to obtain the HPG.
(2) PLA-HPG Synthesis:
dissolving 5g of PLA (polylactic acid) in DCM (dichloromethane in an amount of the smallest volume capable of dissolving PLA), and dissolving 2.3g of HPG in 23ml of DMF (N, N-dimethylformamide), combining the two solutions, and adding a 3A molecular sieve (used after being activated at high temperature) to dry; after drying, the mixture was transferred to a reaction flask, and 0.08mLN, N' -Diisopropylcarbodiimide (DIC) and 13.5mg of 4-Dimethylaminopyridine (DMAP) were added to the reaction flask, followed by stirring at room temperature for 5 days; adding cold ether into the reaction bottle after the reaction for precipitation, collecting the precipitate by centrifugation, dissolving the obtained precipitate in DCM again, precipitating with cold ether again, and finally drying under vacuum for 2 days to obtain the final product.
(3) PLA-Cy5 Synthesis:
dissolving 1.95g of PLA in DCM (the amount is the minimum volume capable of dissolving the PLA), adding 15mg of Cy5 and 0.02ml of IC, stirring and reacting for one day at room temperature, then adding cold ether for precipitation, collecting the precipitate by centrifugation, and drying the obtained precipitate for 2 days under vacuum to obtain the PLA-containing nano-particles.
(4) Respectively preparing a PLA-HPG solution with the concentration of 100mg/mL and a PLA-Cy5 solution with the concentration of 50mg/mL by using EA (ethyl acetate); then adding 0.225mL of PLA-HPG solution, 0.050mL of PLA-Cy5 solution, 0.225mL of EA and 0.350mL of DMSO, uniformly mixing by vortex, transferring the total 0.85mL of mixed solution into 2mL of ultrapure water, then transferring the mixed solution into an ultrasonic crusher while vortex, and carrying out ultrasonic treatment for three times (the power is set to be 65W, the ultrasonic treatment time is 10s, and the mixed solution is immediately placed on ice to be cooled after each ultrasonic treatment) to obtain the nano-emulsion with small volume. Then transferring the small-volume nano-emulsion into 10mL of ultrapure water in a stirring state, and stirring for three minutes; after stirring, the whole solution was transferred to a round bottom flask and rotary evaporated at room temperature until no bubbles were generated, to obtain crude dye-loaded NNPs.
(6) The crude product was transferred to a 15mL, 100kd ultrafiltration tube, centrifuged in a centrifuge (4 ℃,4500rpm, 15min), once centrifuged, washed twice with water, and ultrafiltered three times in total. Adding ultrapure water for rinsing, and washing out NNPs on the inner membrane and the inner wall of the ultrafiltration tube as much as possible to obtain the dye-encapsulated non-adhesive nanoparticle NNPs (NNPs for short, namely non-adhesive NPs).
(7) The redox method is adopted to prepare BNPs (BNP) carrying dyes: adding a volume of sodium periodate solution (0.1 mol/L) into a volume of dye-loaded NNPs, shaking upside down, and reacting for 2-30min; then adding 1 volume of sodium sulfite solution (0.2 mol/L) to terminate the reaction; respectively transferring to an ultrafiltration tube for centrifugation (4 ℃,4500rpm, 15min), centrifuging once, washing twice, and repeating ultrafiltration three times in total; adding ultrapure water for rinsing, and washing out the BNPs (BNPs for short) with the dye entrapped on the ultrafiltration membrane and the inner wall as much as possible to obtain the BNPs with the dye entrapped therein.
(8) The above BNPs were diluted to a concentration of 1.5mg/mL (i.e., 8-fold) using Tris-HCL with a concentration of 5mM, thereby preparing Tris-BNPs nanoparticles.
EXAMPLE 2 preparation of Tris-BNPs nanoparticles (drug-loaded BD)
The preparation method is the same as example 1, and is different from the following steps: PLA-Cy5 is replaced by BD (betamethasone dipropionate), which is called BD/Tris-BNPs for short. NNPs in the preparation process are BD/NNPs, and BNPs are BD/BNPs.
Experimental example 1 permeation Effect of Tris-BNPs into skin
Balb/c mice (purchased from beijing si Bei Fu biotechnology limited, raised for 6-8 weeks to 20-25 g) were painted Imiquimod (IMQ) daily to create a psoriasis mouse model, after 5 days of painting, 0.3mL of PLA-Cy 5-loaded NNPs, BNPs, tris-BNPs solution prepared in example 1 was directly sprayed onto the dorsal skin of a successfully molded psoriasis mouse, then rinsed with water for about 1 minute, the dorsal skin was removed, frozen sections were taken, the frozen tissues were divided into 10 μm sections, mounted on glass slides, and imaged using an EVOS fluorescence microscope, and the pictures were subjected to quantitative fluorescence analysis using Image J.
From the fluorescence photograph of the longitudinal section of the skin on the back of the psoriasis mouse in fig. 1, tris-BNP was able to penetrate the stratum corneum to reach the deep part of the skin as compared to BNPs, indicating that Tris-BNP can penetrate into the epidermis and be retained in the deep part of the skin when applied to the psoriasis skin. Meanwhile, as can be seen from the fluorescence quantification on the longitudinal incision of the skin on the back of the psoriasis mouse in the figure 2, the fluorescence of the Tris-BNPs group has no obvious change, which indicates that the Tris-BNP can go deep into the epidermis when being applied to the psoriasis skin and can be retained in the deep part of the skin, and indicates that the Tris-BNP is expected to become an ideal transdermal tool for treating psoriasis.
Experimental example 2 Retention of Tris-BNPs in skin
Balb/c mice (purchased from Beijing Bei Fu Biotechnology Limited, raised for 6-8 weeks to 20-25 g) were painted Imiquimod (IMQ) daily to create a psoriasis mouse model, and after 5 days of painting, 0.3mL of the PLA-Cy 5-loaded NNPs, BNPs, tris-BNPs solution prepared in example 1 was directly applied to the dorsal skin of a successfully molded psoriasis mouse, followed by rinsing with water for about 1 minute. To better understand the retention and permeation of various nanoparticles in the skin, the fluorescence distribution of the skin on the back of psoriatic mice at various time points (5min, 1day,2day,3day, respectively) was observed using a small animal in vivo imager (Perkin Elmer small animal in vivo imaging System, model Lumina XR Series III). And simultaneously, photographing under a small animal living body imager aiming at each time point, and carrying out fluorescence quantitative analysis on the small animal living body imager according to the ROI corresponding to the fluorescence area. In addition, the fluorescence intensity at different time points is also quantified by small animal living body imaging processing software (imager complete software).
As can be seen from fig. 3 and 4, the NNPs and BNPs decreased significantly (85% and 50% respectively) within 1day and disappeared completely within 2 days, and the NNPs may decrease with renewal of skin cells because it did not bioadhesion to the epidermis. The disappearance of BNPs from psoriatic skin was consistent with the time required for IMQ to induce the loss of white skin from psoriatic mice, indicating that they did not penetrate deep into psoriatic skin. And the Tris-BNPs disappear from the skin after 4 days, which is consistent with the proliferation period (4-5 days) of the psoriasis keratocytes passing through the epidermis, and the retention effect of the Tris-BNP is better than that of other nanoparticles.
EXAMPLE 3 therapeutic Effect of Tris-BNPs on psoriasis mice
The method comprises the steps of smearing IMQ on balb/c mice every day to establish a Psoriasis mouse model, after smearing for 6 days, randomly dividing the Psoriasis mice successfully modeled into 5 groups [ BD/NNPs, BD/BNPs, BD/Tris-BNPs, BD infection (BD ointment) group and untreated and healthy groups ], treating (0.3 mL) the back skin of each group of mice on the sixth day by using drenches (BD/NNPs, BD/BNPs and BD/BNTris-Ps), applying BD infection in a smearing mode (uniformly smearing affected parts), observing the change condition of the back skin of each group of mice, and evaluating the severity of diseases by using Psoriasis area indexes (Psoriasis area and severity index, PASI) every day. In addition, the body weight of the mice was recorded every day, and the change in the body weight of the mice was observed.
The change of the dorsal skin of each group of mice was observed on the ninth day, and it can be seen from FIG. 5 that the BD/Tris-BNPs group was closest to the skin of the mice in the healthy group and had a better therapeutic effect than the other groups.
Meanwhile, as can be seen from fig. 6, repeated application of the IMQ cream to the skin of the back of the mouse for 6 consecutive days induces skin lesions such as erythema, scaling, and skin thickness enhancement. If left untreated, the cumulative PASI score will gradually increase by 11 to day 9 depending on the clinical symptoms and severity of psoriasis symptoms in the model mice. The use of BD/Tris-BNPs greatly improved the severity of the disease compared to psoriatic mice without any treatment, or compared to mice treated by using BD/NNPs and BD/BNPs. It was shown that BD/Tris-BNPs could penetrate the epidermis, remaining in the skin for at least 3 days. Meanwhile, it can be seen from the PASI score that the treatment effect of the traditional topical therapy of BD (betamethasone dipropionate) alone is not very good compared with BD/Tris-BNPs, while the treatment of BD/Tris-BNPs shows better anti-inflammatory effect and only one dose in 3 days (namely only one dose is applied in 3 days). The fact that Tris gradually leaves along with the penetration of BNPs into tissues is proved that the surface of BNPs contains abundant aldehyde groups which can react with the tissues to generate amino groups so that nanoparticles are stably retained on the tissues, thus the nanoparticles can be retained in the deep part of the skin, release the drugs slowly and controllably, the drug dosage and the drug action time are prolonged, and the treatment effect is further improved.
In addition, as can be seen from the change in body weight of the mice from the modeling of the psoriasis mice to the drug treatment in FIG. 7, the body weight of the mice in the BD/NNPs, BD/BNPs and BD ointment treatment groups decreased, while the body weight of the mice treated with BD/Tris-BNPs gradually increased, indicating that the psoriasis mice treated with BD/Tris-BNPs had better treatment effect, resulting in the increase in body weight of the mice.
It can be seen from the comprehensive experimental examples 1 and 2 that Tris-BNPs developed on the basis of PLA-HPG bioadhesive nanoparticles can well penetrate through the stratum corneum of psoriatic skin and deeply penetrate into the skin, and in-vivo and in-vitro experiments also prove that Tris gradually leaves along with the penetration of BNPs into tissues, so that BNPs are finally restored into bioadhesive nanoparticles, and therefore the BNPs can be retained in the deep skin, release a medicament in a sustained and controlled manner, the medicament dosage is prolonged, and a better treatment effect is achieved.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (6)
1. A preparation method of Tris-BNP nano-particles is characterized by comprising the following steps:
s1, PLA-HPG synthesis: dissolving PLA in DCM, dissolving HPG in DMF, combining the two solutions, drying, adding N, N' -diisopropyl carbodiimide and 4-dimethylamino pyridine, and stirring for reaction at room temperature for 4-6 days; after reaction, the product is prepared by precipitation;
s2, respectively preparing a PLA-HPG solution and a medicine solution by using EA, wherein the medicine is an external medicine for treating the skin diseases, the external medicine for treating the skin diseases is betamethasone dipropionate, the concentration of the PLA-HPG solution is 100mg/mL, the concentration of the medicine solution is 50mg/mL, and then mixing the PLA-HPG solution, the medicine solution, the EA and the DMSO according to a ratio of 0.225:0.050:0.225: uniformly mixing the mixture in a volume ratio of 0.350, transferring the mixture into a certain amount of water, performing ultrasonic treatment for three times to obtain a small-volume nanoemulsion, transferring the small-volume nanoemulsion into the water in a stirring state again, evaporating the small-volume nanoemulsion until no bubbles are generated to obtain a crude product of the drug/NNPs, and purifying the crude product by an ultrafiltration tube to obtain the drug/NNPs;
s3, adding a sodium periodate solution into the medicines/NNPs to react for 2-30min; adding sodium sulfite solution to stop reaction, and purifying by an ultrafiltration tube to obtain bioadhesive nano-particle medicines/BNPs for treating skin diseases;
and S4, properly diluting the drug/BNPs obtained in the step S3 by using Tris-HCL to prepare Tris-BNPs nanoparticles.
2. The method of claim 1, wherein the concentration of Tris-HCL is 5mM.
3. The method of claim 1, wherein Tris-HCL is used to dilute the drug/BNPs to a concentration of 1.0-2.0 mg/mL.
4. Tris-BNP nanoparticles prepared by the method for preparing Tris-BNP nanoparticles as claimed in claims 1 to 3.
5. The use of the Tris-BNP nanoparticles of claim 4 in the preparation of a medicament for the treatment of skin disorders.
6. Use of Tris-BNP nanoparticles according to claim 5 for the preparation of a medicament for the treatment of a skin disorder, wherein said skin disorder is psoriasis.
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