Bionic polypeptide nano-composite skin permeation carrier and preparation method thereof
By constructing a covalently bonded outer shell of biomimetic transmembrane peptides and bioadhesive peptides on the surface of the nanocore, the problems of insufficient penetration ability, drug loading capacity and stability of existing transdermal carriers are solved, and efficient and stable drug delivery is achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SUZHOU SHUSHU MEDICAL TECH CO LTD
- Filing Date
- 2026-02-07
- Publication Date
- 2026-05-12
AI Technical Summary
Existing transdermal delivery systems have shortcomings in terms of penetration ability, drug loading capacity, and stability. Furthermore, conventional physical permeation enhancement methods are either invasive or complex to operate, making it difficult to achieve safe, continuous, and non-invasive skin delivery.
A biomimetic polypeptide nanocomposite skin permeation carrier is used. By mimicking the natural mechanism of skin permeation and adhesion, biomimetic membrane-penetrating peptides and bioadhesive peptides are covalently fixed on the surface of the nanocore to construct a biomimetic shell with cell membrane penetration ability and skin surface adhesion ability.
It significantly improved encapsulation efficiency and drug loading, increased steady-state transdermal rate, reduced drug leakage rate, enhanced skin delivery performance and biocompatibility, and achieved efficient and stable drug delivery.
Smart Images
Figure CN122005833A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, and in particular to a biomimetic polypeptide nanocomposite skin permeation carrier and its preparation method. Background Technology
[0002] Transdermal drug delivery and skin repair formulations have wide applications in drug delivery, cosmetic care, and topical treatment. However, the dense structure and low permeability of the stratum corneum limit the effective penetration and deep absorption of most active ingredients. Existing transdermal carriers mainly include liposomes, nanoemulsions, and polymer nanoparticles. While they can improve drug dissolution and stability to some extent, they generally suffer from insufficient penetration, limited drug loading, poor skin retention, and easy leakage during storage. In addition, conventional physical permeation-enhancing methods such as microneedling and electroporation have drawbacks such as being invasive or complex to operate, making it difficult to achieve safe, continuous, and non-invasive skin delivery.
[0003] In recent years, biomimetic peptides have become an important strategy for improving skin penetration and targeted delivery due to their excellent cell membrane permeability, biodegradability, and low immunogenicity. However, carriers modified with single transmembrane peptides are easily diluted or cleared by sweat and sebum during transdermal delivery, resulting in insufficient effective delivery. On the other hand, although bioadhesive peptides can enhance adhesion to the skin surface, they lack active penetration ability, making it difficult to achieve deep delivery.
[0004] Therefore, there is an urgent need for a biomimetic nanocarrier system that combines high drug loading efficiency, active penetration and long-lasting adhesion properties to achieve efficient encapsulation and deep transdermal delivery of hydrophobic active ingredients, improve drug utilization and enhance the therapeutic and care effects of skin treatments. Summary of the Invention
[0005] To address the aforementioned issues, this invention proposes a biomimetic polypeptide nanocomposite skin permeation carrier and its preparation method. By mimicking the natural mechanisms of skin penetration and adhesion, this invention achieves efficient encapsulation, steady-state release, and deep delivery of active ingredients.
[0006] This invention proposes a biomimetic polypeptide nanocomposite skin permeation carrier and its preparation method, comprising the following steps:
[0007] Step 1: Dissolve the hydrophobic active ingredient and the biodegradable polymer material together in an organic solvent to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing a stabilizer. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain a nanocore loaded with the active ingredient.
[0008] Step 2: In the presence of activator and condensing agent, the nanocore is co-incubated with biomimetic membrane-penetrating peptides and bioadhesion peptides in 2-morpholine ethanesulfonic acid buffer at pH 7.0-7.6 to carry out an amidation reaction, so that the peptides are fixed on the surface of the nanocore by covalent bonds to form a biomimetic functionalized shell.
[0009] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0010] Preferably, in step 1, the mass ratio of the hydrophobic active ingredient to the biodegradable polymer material is 1:(5-15).
[0011] Preferably, the biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer, chitosan, and hyaluronic acid.
[0012] Preferably, the organic solvent in step 1 is one or more of acetone, acetonitrile, or dimethyl sulfoxide.
[0013] Preferably, the stabilizer in step 1 is polyvinyl alcohol or poloxamer.
[0014] Preferably, the volume ratio of the oil phase to the water phase in step 1 is 1:(3-5).
[0015] Preferably, in step 2, the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and the condensing agent is N-hydroxysuccinimide.
[0016] Preferably, the amidation reaction in step 2 is carried out at a temperature of 10-25°C for 2-6 hours.
[0017] Preferably, in step 2, the mass ratio of the nanocore, the biomimetic membrane-penetrating peptide, and the bioadhesive peptide is 1:(0.05-0.2):(0.05-0.3).
[0018] The beneficial effects of this invention are:
[0019] This invention employs a dual-functional synergistic modification strategy of "biomimetic membrane-penetrating peptide + bioadhesive peptide" to construct a biomimetic shell on the surface of a nanocore, possessing both cell membrane penetration and skin surface adhesion capabilities. Covalent fixation of the peptides is achieved through a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride / N-hydroxysuccinimide coupling system, enabling the carrier to simultaneously possess active permeation and steady-state retention properties. This composite carrier significantly improves encapsulation efficiency and drug loading (approximately 35% higher than the unmodified sample), increases the steady-state transdermal rate by approximately 2.5 times, and reduces drug leakage to one-third of the original rate. The dual-peptide shell effectively prevents nanocore aggregation, slows drug diffusion, and improves the long-term storage stability and transdermal efficiency of the carrier, demonstrating excellent skin delivery performance and biocompatibility. Attached Figure Description
[0020] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:
[0021] Figure 1 Encapsulation efficiency and drug loading;
[0022] Figure 2 For steady-state transdermal rate;
[0023] Figure 3 The changes in drug leakage rate and particle size after 30 days are shown. Detailed Implementation
[0024] The following provides a detailed description of the embodiments of the present invention: These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and processes. However, the scope of protection of the present invention is not limited to the following embodiments. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions.
[0025] In the embodiments, curcumin was used as a model drug to verify the encapsulation efficiency, drug loading and transdermal performance of the carrier, but this should not be construed as a limitation on the scope of protection of the present invention.
[0026] Example 1
[0027] A method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier includes the following steps:
[0028] Step 1: Dissolve 5 g of curcumin and 25 g of polylactic acid-glycolic acid copolymer in 10 mL of acetone to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 30 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0029] Step 2: In the presence of 0.2 g 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g N-hydroxysuccinimide, 5 g nanocore, 0.25 g biomimetic membrane-penetrating peptide, and 0.25 g bioadhesion peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.0 and amidation reaction was carried out at 10 °C for 2 h, so that the peptides were covalently fixed on the surface of the nanocore to form a biomimetic functionalized shell;
[0030] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0031] Example 2
[0032] A method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier includes the following steps:
[0033] Step 1: Dissolve 5 g curcumin and 75 g chitosan in 10 mL acetonitrile to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) poloxamer, with 10 mL of oil phase and 50 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain the nanocore loaded with active ingredients.
[0034] Step 2: In the presence of 0.2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g of N-hydroxysuccinimide, 5 g of nanocore, 1 g of biomimetic membrane-penetrating peptide, and 1.5 g of bioadhesive peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.6 and amidation reaction was carried out at 25°C for 6 h, so that the peptide was fixed on the surface of the nanocore by covalent bonds to form a biomimetic functionalized shell;
[0035] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0036] Example 3
[0037] A method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier includes the following steps:
[0038] Step 1: Dissolve 5 g curcumin and 50 g hyaluronic acid together in 10 mL of dimethyl sulfoxide to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 40 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0039] Step 2: In the presence of 0.2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g of N-hydroxysuccinimide, 5 g of nanocore, 0.625 g of biomimetic membrane-penetrating peptide, and 0.875 g of bioadhesion peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.3 and amidation reaction was carried out at 20°C for 4 h, so that the peptides were covalently fixed on the surface of the nanocore to form a biomimetic functionalized shell;
[0040] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0041] Example 4
[0042] A method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier includes the following steps:
[0043] Step 1: Dissolve 5 g curcumin and 75 g chitosan together in 10 mL acetone to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 50 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0044] Step 2: In the presence of 0.2 g 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g N-hydroxysuccinimide, 5 g nanocore, 0.25 g biomimetic membrane-penetrating peptide, and 0.25 g bioadhesion peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.6 and amidation reaction was carried out at 25°C for 2 h, so that the peptides were covalently fixed on the surface of the nanocore to form a biomimetic functionalized shell;
[0045] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0046] Comparative Example 1: The difference between this comparative example and Example 1 is that no biomimetic membrane-penetrating peptides and bioadhesion peptides are added.
[0047] Step 1: Dissolve 5 g of curcumin and 25 g of polylactic acid-glycolic acid copolymer in 10 mL of acetone to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 30 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0048] Step 2: The nanocore is redispersed in a freeze-drying protectant and then freeze-dried to obtain a nanocomposite skin penetration carrier.
[0049] Comparative Example 2: The difference between this comparative example and Example 1 is that no biomimetic membrane-penetrating peptide is added.
[0050] Step 1: Dissolve 5 g of curcumin and 25 g of polylactic acid-glycolic acid copolymer in 10 mL of acetone to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 30 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0051] Step 2: In the presence of 0.2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g of N-hydroxysuccinimide, 5 g of nanocore and 0.25 g of bioadhesive peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.0 and amidation reaction was carried out at 10°C for 2 h, so that the peptide was fixed on the surface of the nanocore by covalent bonds to form a biomimetic functionalized shell;
[0052] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0053] Comparative Example 3: The difference between this comparative example and Example 1 is that no bioadhesion peptides are added.
[0054] Step 1: Dissolve 5 g of curcumin and 25 g of polylactic acid-glycolic acid copolymer in 10 mL of acetone to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing 1% (W / V) polyvinyl alcohol, with 10 mL of oil phase and 30 mL of aqueous phase. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain nanocore loaded with active ingredients.
[0055] Step 2: In the presence of 0.2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.06 g of N-hydroxysuccinimide, 5 g of nanocore and 0.25 g of biomimetic membrane-penetrating peptide were co-incubated in 2-morpholine ethanesulfonic acid buffer at pH 7.0 and amidation reaction was carried out at 10 °C for 2 h, so that the peptide was fixed on the surface of the nanocore by covalent bonds to form a biomimetic functionalized shell;
[0056] Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
[0057] Performance testing
[0058] 1. Encapsulation efficiency and drug loading
[0059] Add the sample to an ultrafiltration centrifuge tube and centrifuge at 10,000 rpm for 30 min. The filtrate contains free drug. Accurately measure a certain volume of supernatant or filtrate (denoted as V). 游离 After appropriate dilution with methanol, the drug concentration was determined by high-performance liquid chromatography (HPLC). 游离 Another 1.0 mL aliquot of the nanocarrier suspension was precisely measured, and 10 mL of methanol was added. The mixture was vortexed for 10 min to completely destroy the nanostructure and dissolve the drug. After filtration through a 0.22 μm microporous membrane, the total drug concentration was determined by high-performance liquid chromatography (HPLC). 总 Encapsulation ratio = [(C)] 总 ×V 总 )-(C 游离 ×V 游离 )] / (C 总 ×V 总 ) × 100%, Drug loading = [(C 总 ×V 总 )-(C 游离 ×V 游离 The test results are shown in Table 1, calculated as 100% of the dry weight of the nanoparticles.
[0060] Table 1 Encapsulation efficiency and drug loading test data
[0061] sample Encapsulation rate (%) Drug loading (% w / w) Example 1 78.20 13.33 Example 2 82.18 13.64 Example 3 85.15 14.18 Example 4 80.16 13.79 Comparative Example 1 49.03 10.05 Comparative Example 2 70.32 11.60 Comparative Example 3 68.27 10.31
[0062] As shown in Table 1, the encapsulation efficiency and drug loading of Examples 1-4 were at a high level (85.15%, 14.18% w / w), significantly better than all comparative examples. This indicates that the nanocore can effectively encapsulate curcumin, and the subsequent peptide modification process has little impact on the pre-encapsulated drug. In contrast, Comparative Example 1, without the addition of biomimetic membrane-penetrating peptides and bioadhesion peptides, had an encapsulation efficiency of only 49.03% and a drug loading of 10.05% w / w. This is because the lack of a peptide shell makes the drug more likely to leak from the core during purification and storage. Simultaneously, the lack of surface modification resulted in slightly lower stability of the nanoparticles during preparation, leading to lower initial encapsulation efficiency compared to other examples. Comparative Examples 2 and 3, without the addition of biomimetic membrane-penetrating peptides and bioadhesion peptides respectively, had encapsulation efficiency and drug loading lower than Examples 1-4. The effect of single peptide modification was not as complete as that of dual-peptide synergistic modification. The absence of any peptide may lead to an unstable and non-dense shell structure, resulting in partial drug leakage during purification and testing.
[0063] 2 Transdermal performance
[0064] Fresh, detached pig skin was collected, subcutaneous fat was removed, and the skin was rinsed thoroughly with physiological saline. It was then stored at -20°C and thawed before use. The skin was placed between the supply chamber and the receiving chamber, with the stratum corneum facing the supply chamber. The receiving chamber was filled with phosphate-buffered saline solution at pH 7.4 and continuously stirred magnetically to maintain a constant temperature of 37°C. A certain volume of nanocarrier suspension was added to the supply chamber. At predetermined time points (e.g., 2, 4, 6, 8, 12, 24 h), all the receiving fluid was removed from the receiving chamber, and an isothermal and equal volume of fresh receiving fluid was immediately added. The drug concentration in the removed receiving fluid was determined by high-performance liquid chromatography (HPLC). n The cumulative transdermal drug delivery rate (Q) was calculated by measuring the drug concentration in the receiving fluid at different time points. n Then, plot the cumulative transdermal volume against time, take the slope of the steady-state linear portion of the curve, divide it by the effective skin diffusion area (A), and finally obtain the steady-state transdermal rate (J). ss =Slope / A). The formula for calculating cumulative transdermal dose is:
[0065] The test results are shown in Table 2:
[0066] Table 2 Transdermal Performance Test Data
[0067] sample Steady-state transdermal rate (μg / cm² / h) Example 1 3.18 Example 2 3.53 Example 3 3.74 Example 4 3.25 Comparative Example 1 1.16 Comparative Example 2 2.02 Comparative Example 3 1.51
[0068] As shown in Table 2, Examples 1-4 achieved a transdermal transdermal rate of 3.74 μg / cm² / h thanks to the powerful synergistic effect of their dual-functional biomimetic shells. Comparative Example 1, however, had the lowest transdermal transdermal rate. This was because the nanoparticles lacked the ability to actively penetrate the skin barrier and remain on the skin surface for extended periods, relying solely on passive diffusion, resulting in extremely low efficiency. Comparative Example 2 also exhibited a poor transdermal transdermal rate. Lacking membrane-penetrating peptides, its transdermal efficiency primarily depended on the slow release of the drug after adhesion and passive diffusion, thus limiting its effectiveness. Comparative Example 3 lacked bioadhesive peptides, preventing the nanocarrier from effectively interacting with the skin and initiating the penetration process. It was easily removed or dispersed, leading to a significant reduction in penetration efficiency.
[0069] 3. Particle size variation and drug leakage rate
[0070] (1) Particle size variation: The lyophilized powder of the nanocomposite carrier was redispersed with deionized water to prepare a 1 mg / mL nanocarrier suspension. The initial particle size (D0) of each sample after redispersement was measured at 25℃ using a dynamic light scattering instrument and recorded as D0. Each sample suspension was aliquoted into sealed sample bottles and stored in a constant temperature environment at 4℃, avoiding light and vibration during storage. On the 30th day of storage, the sample was taken out and gently vortexed to mix. The particle size (D0) was measured under the same conditions using a dynamic light scattering instrument. 30 Each sample should be tested in at least three parallel trials, and the average value should be taken. Particle size variation (nm) = D 30 -D0.
[0071] (2) Drug leakage rate: The lyophilized nanocomposite carrier powder was redispersed with deionized water to prepare a nanocarrier suspension of 1 mg / mL. At the beginning of storage (day 0), 1.0 mL of the nanocarrier suspension was taken, 10 mL of methanol was added, and the nanostructure was destroyed by vortexing for 10 min. After filtration through a 0.22 μm filter membrane, the total drug concentration C0 was determined by high performance liquid chromatography. On day 30, 1.0 mL of the sample suspension was taken and placed in an ultrafiltration centrifuge tube (e.g., with a molecular weight cutoff of 100 kDa), and centrifuged at 10,000 rpm for 30 min. The filtrate (containing free drug) was collected, and the drug concentration C0 was determined by high performance liquid chromatography. 游离 Take another 1.0 mL sample, completely destroy the nanostructure with methanol, and then determine the total drug concentration C. 总 Drug penetration rate (%) = C 游离 / C 总 ×100%. Each sample should be tested at least three times in parallel, and the average value should be taken. The test results are shown in Table 3:
[0072] Table 3. Test data on particle size variation and drug leakage rate
[0073] sample Drug leakage rate (%) Particle size variation (nm) Example 1 8.12 +8.4 Example 2 7.11 +10.6 Example 3 6.14 +14.8 Example 4 5.07 +13.5 Comparative Example 1 20.25 +51.2 Comparative Example 2 12.13 +38.1 Comparative Example 3 15.20 +28.9
[0074] As shown in Table 3, the drug leakage rate of Examples 1-4 was as low as 5.07%, with the smallest particle size change (+8.4 nm), indicating the best long-term stability. The covalently bonded dipeptide shell formed a dense protective layer, effectively preventing the aggregation of the nanocore and the leakage of the internal drug. In contrast, the exposed nanocore of Comparative Example 1 had a high surface energy, making it prone to aggregation and resulting in a significant increase in particle size. Furthermore, without the physical barrier of the shell, the drug continued to diffuse out during storage, leading to a high leakage rate. Comparative Examples 2 and 3 only had single peptide modification, and the protective effect of the shell structure was weaker than that of a complete dipeptide shell, resulting in a higher drug leakage rate and a larger particle size variation.
[0075] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. A method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier, characterized in that, Includes the following steps: Step 1: Dissolve the hydrophobic active ingredient and the biodegradable polymer material together in an organic solvent to prepare an oil phase. Add the oil phase dropwise to an aqueous phase containing a stabilizer. After the addition is complete, continue stirring to evaporate and remove the organic solvent. Centrifuge and wash to obtain a nanocore loaded with the active ingredient. Step 2: In the presence of activator and condensing agent, the nanocore is co-incubated with biomimetic membrane-penetrating peptide and bioadhesion peptide in 2-morpholine ethanesulfonic acid buffer at pH 7.0-7.6 to carry out amidation reaction, so that the peptide is fixed on the surface of the nanocore by covalent bonds to form a biomimetic functional shell. Step 3: After the reaction is complete, the product solution is purified by ultrafiltration and centrifugation to remove unreacted peptides and reagents. Finally, the purified nanocomposite carrier is redispersed in a freeze-drying protectant and freeze-dried to obtain a biomimetic peptide nanocomposite skin penetration carrier.
2. The preparation method of the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, In step 1, the mass ratio of the hydrophobic active ingredient to the biodegradable polymer material is 1:(5-15).
3. The preparation method of the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 2, characterized in that, The biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer, chitosan, and hyaluronic acid.
4. The preparation method of the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, The organic solvent in step 1 is one or more of acetone, acetonitrile, or dimethyl sulfoxide.
5. The method for preparing the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, The stabilizer in step 1 is polyvinyl alcohol or poloxamer.
6. The method for preparing the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, In step 1, the volume ratio of the oil phase to the water phase is 1:(3-5).
7. The method for preparing the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, In step 2, the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and the condensing agent is N-hydroxysuccinimide.
8. The method for preparing the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, The amidation reaction in step 2 is carried out at a temperature of 10-25°C for 2-6 hours.
9. The method for preparing the biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, characterized in that, In step 2, the mass ratio of the nanocore, biomimetic membrane-penetrating peptide, and bioadhesive peptide is 1:(0.05-0.2):(0.05-0.3).