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CN-122005833-A - Bionic polypeptide nano-composite skin permeation carrier and preparation method thereof

CN122005833ACN 122005833 ACN122005833 ACN 122005833ACN-122005833-A

Abstract

The invention discloses a bionic polypeptide nano-composite skin permeation carrier and a preparation method thereof. The carrier takes biodegradable polymer material as a nano core, loads hydrophobic active ingredients, and forms a nano composite system with a difunctional bionic shell through covalent fixation of bionic membrane penetrating peptide and bioadhesion peptide. The preparation method comprises three steps of oil/water emulsification, volatilization nucleation, peptide coupling modification and freeze drying. The obtained carrier has the characteristics of active penetration of skin barrier and long-acting residence, the encapsulation rate is more than 85%, the steady-state transdermal rate is improved to 3.7 mug/cm < 2 >/h, and the drug leakage rate is lower than 7% after 30 days of storage. The invention realizes high-efficiency encapsulation, steady-state release and deep delivery of active ingredients by simulating the natural mechanism of skin permeation and adhesion, is suitable for the fields of transdermal drug delivery, skin repair, cosmetology and the like, and has good application prospect and industrialization potential.

Inventors

  • WU CHANGLIANG
  • LI CAIJUN
  • Wu Yulanxin

Assignees

  • 苏州术数医疗科技有限公司

Dates

Publication Date
20260512
Application Date
20260207

Claims (9)

  1. 1. The preparation method of the bionic polypeptide nano-composite skin permeation carrier is characterized by comprising the following steps of: step 1, dissolving a hydrophobic active ingredient and a biodegradable polymer material in an organic solvent together to prepare an oil phase, dropwise adding the oil phase into a water phase containing a stabilizer, continuously stirring after the dropwise adding is finished to volatilize and remove the organic solvent, centrifuging, and washing to obtain a nano core loaded with the active ingredient; step 2, incubating the nano-core, the bionic membrane penetrating peptide and the bioadhesion peptide in a 2-morpholinoethanesulfonic acid buffer solution with the pH of 7.0-7.6 together in the presence of an activating agent and a condensing agent, and performing amidation reaction to fix the polypeptide on the surface of the nano-core through a covalent bond to form a bionic functional shell; And 3, after the reaction is finished, carrying out ultrafiltration centrifugal purification on the product solution to remove unreacted polypeptide and reagent, and finally, re-dispersing the purified nano composite carrier in a freeze-drying protective agent, and carrying out freeze drying to obtain the bionic polypeptide nano composite skin permeation carrier.
  2. 2. The method for preparing the bionic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the mass ratio of the hydrophobic active ingredient to the biodegradable polymer material in the step 1 is 1 (5-15).
  3. 3. The method for preparing the bionic polypeptide nanocomposite skin permeation carrier according to claim 2, wherein the biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer, chitosan and hyaluronic acid.
  4. 4. The method for preparing the bionic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the organic solvent in the step 1 is one or more of acetone, acetonitrile and dimethyl sulfoxide.
  5. 5. The method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the stabilizer in the step 1 is polyvinyl alcohol or poloxamer.
  6. 6. The method for preparing the bionic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the volume ratio of the oil phase to the water phase in the step 1 is 1 (3-5).
  7. 7. The method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the activator in the step 2 is 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride) and the condensing agent is N-hydroxysuccinimide.
  8. 8. The method for preparing a biomimetic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the amidation reaction in the step 2 is performed at a temperature of 10-25 ℃ for a time of 2-6 h.
  9. 9. The method for preparing the bionic polypeptide nanocomposite skin permeation carrier according to claim 1, wherein the mass ratio of the nano-core to the bionic membrane-penetrating peptide to the bioadhesion peptide in the step 2 is 1 (0.05-0.2): 0.05-0.3.

Description

Bionic polypeptide nano-composite skin permeation carrier and preparation method thereof Technical Field The invention relates to the technical field of biomedicine, in particular to a bionic polypeptide nano-composite skin permeation carrier and a preparation method thereof. Background Transdermal administration and skin repair formulations have wide application in the field of drug delivery, cosmetic care and topical treatment. However, the stratum corneum structure of the skin is dense, low in permeability, limiting the effective penetration and deep absorption of most active ingredients. The existing transdermal carrier mainly comprises liposome, nanoemulsion, polymer nanoparticles and the like, which can improve the dissolution and stability of the drug to a certain extent, but generally have the problems of insufficient penetrating power, limited drug loading, poor skin retention, easy leakage of the drug in the storage process and the like. In addition, conventional physical permeation promotion methods such as microneedles, electroporation, and the like have the disadvantages of being invasive or complex to operate, and the like, and it is difficult to achieve safe, continuous, non-invasive skin delivery. In recent years, biomimetic polypeptides are an important strategy for improving skin permeation and targeted delivery due to their excellent cell membrane penetrability, biodegradability and low immunogenicity. However, single transmembrane peptide modified vehicles are susceptible to dilution or clearance by sweat, sebum, and the like during the transdermal process, resulting in insufficient effective delivery. On the other hand, bioadhesive peptides, while enhancing skin surface adhesion, lack active penetration capabilities and make deep delivery difficult. Therefore, there is a need for a biomimetic nanocarrier system with high drug delivery efficiency, active penetration and durable adhesion properties to achieve efficient encapsulation and deep transdermal delivery of hydrophobic active ingredients, improve drug availability and enhance skin treatment and care effects. Disclosure of Invention Aiming at the problems, the invention provides a bionic polypeptide nano-composite skin permeation carrier and a preparation method thereof, the invention realizes high-efficiency encapsulation, steady-state release and deep delivery of active ingredients by simulating the natural mechanism of skin permeation and adhesion. The invention provides a bionic polypeptide nano-composite skin permeation carrier and a preparation method thereof, comprising the following steps: step 1, dissolving a hydrophobic active ingredient and a biodegradable polymer material in an organic solvent together to prepare an oil phase, dropwise adding the oil phase into a water phase containing a stabilizer, continuously stirring after the dropwise adding is finished to volatilize and remove the organic solvent, centrifuging, and washing to obtain a nano core loaded with the active ingredient; step 2, incubating the nano-core, the bionic membrane penetrating peptide and the bioadhesion peptide in a 2-morpholinoethanesulfonic acid buffer solution with the pH of 7.0-7.6 together in the presence of an activating agent and a condensing agent, and performing amidation reaction to fix the polypeptide on the surface of the nano-core through a covalent bond to form a bionic functional shell; And 3, after the reaction is finished, carrying out ultrafiltration centrifugal purification on the product solution to remove unreacted polypeptide and reagent, and finally, re-dispersing the purified nano composite carrier in a freeze-drying protective agent, and carrying out freeze drying to obtain the bionic polypeptide nano composite skin permeation carrier. Preferably, the mass ratio of the hydrophobic active ingredient to the biodegradable polymer material in the step 1 is 1 (5-15). Preferably, the biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer, chitosan and hyaluronic acid. Preferably, the organic solvent in the step 1 is one or more of acetone, acetonitrile or dimethyl sulfoxide. Preferably, the stabilizer in the step 1 is polyvinyl alcohol or poloxamer. Preferably, the volume ratio of the oil phase to the water phase in the step 1 is 1 (3-5). Preferably, the activator in the step 2 is 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, and the condensing agent is N-hydroxysuccinimide. Preferably, the amidation reaction in the step 2 is carried out at a temperature of 10-25 ℃ for a time of 2-6 h. Preferably, in the step 2, the mass ratio of the nano-core, the bionic membrane penetrating peptide and the bioadhesion peptide is 1 (0.05-0.2) to 0.05-0.3. The beneficial effects of the invention are as follows: The invention adopts a double-function cooperative modification strategy of bionic membrane penetrating peptide and bioadhesion peptide to construct a bionic shell with cell membrane penet