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CN-121987586-A - Curcumin-loaded targeted cell membrane derived vesicle delivery system and application thereof

CN121987586ACN 121987586 ACN121987586 ACN 121987586ACN-121987586-A

Abstract

The invention discloses a curcumin-loaded targeting cell membrane derivative vesicle delivery system and application thereof, and belongs to the field of biological medicines. A curcumin-loaded targeted cell membrane derived vesicle delivery system comprises a cell membrane vesicle, IETP2 ear targeting polypeptides modified on the surface of the cell membrane vesicle, and curcumin encapsulated inside the cell membrane vesicle. Compared with the prior art, the curcumin targeting delivery system has the advantages that curcumin is controlled by regulating cAMP/PKA/CREB channels, mitochondrial functions are improved, oxidative stress and apoptosis are inhibited to prevent and treat drug-induced deafness, IETP2 polypeptide modified cell membrane derived vesicles are used as the targeting delivery system of curcumin, accumulation of drugs in cochlea is remarkably improved, and animal models prove that the delivery system has stronger hearing protection effect and better biosafety compared with free curcumin.

Inventors

  • FANG QIAOJUN
  • YANG JIANMING
  • CAO WEI
  • DU JIAWEI
  • PAN SHIYI

Assignees

  • 安徽医科大学第二附属医院

Dates

Publication Date
20260508
Application Date
20260402

Claims (10)

  1. 1. A curcumin-loaded targeted cell membrane derived vesicle delivery system comprising: Cell membrane vesicles; an IETP2 ear targeting polypeptide modified on the surface of the cell membrane vesicle; and curcumin encapsulated inside the cell membrane vesicles.
  2. 2. The delivery system of claim 1, wherein the material of the cell membrane vesicles is derived from a cochlear hair cell line.
  3. 3. The delivery system of claim 1, wherein the curcumin is present in free form or encapsulated within a polymer nanoparticle within a cell membrane vesicle, the polymer nanoparticle being a polylactic acid-glycolic acid copolymer nanoparticle.
  4. 4. The delivery system of claim 1, wherein the IETP2 ear targeting polypeptide is grafted to Mal-PEG2k-DSPE phospholipid by chemical modification and modified at the surface of the cell membrane vesicle by two-person assembly.
  5. 5. The delivery system of claim 1, wherein the mass ratio of IETP2 ear targeting polypeptide to cell membrane material is from 1:20 to 1:200.
  6. 6. A method of preparing a delivery system according to any one of claims 1 to 5, comprising the steps of: extracting HEI-OC1 cell membrane, and preparing cell membrane vesicle by extrusion or ultrasonic method; grafting IETP2 polypeptide on Mal-PEG2k-DSPE phospholipid by a chemical modification method, and modifying the surface of the cell membrane vesicle by two self-assembly methods to obtain a targeting vesicle carrier; Curcumin is encapsulated in the targeting vesicle carrier by adopting a liposome extrusion method.
  7. 7. A pharmaceutical composition comprising a delivery system according to any one of claims 1 to 5, and a pharmaceutically acceptable carrier, excipient or adjuvant.
  8. 8. The pharmaceutical composition of claim 7, further comprising at least one active ingredient selected from the group consisting of antioxidants, anti-inflammatory agents, hormonal agents, and other hearing protection agents, wherein the active ingredient comprises dexamethasone or N-acetylcysteine.
  9. 9. Use of a delivery system according to any one of claims 1 to 5 or a pharmaceutical composition according to any one of claims 7 to 8 for the preparation of a medicament for the prevention and treatment of deafness or hearing loss.
  10. 10. The use according to claim 9, wherein the deafness is aminoglycoside antibiotic, cisplatin chemotherapeutic or diuretic induced deafness; And the delivery system functions by activating cAMP/PKA/CREB signaling pathways, improving mitochondrial function, and inhibiting cochlear hair cell apoptosis.

Description

Curcumin-loaded targeted cell membrane derived vesicle delivery system and application thereof Technical Field The invention relates to the field of biological medicine, in particular to a curcumin-loaded targeting cell membrane derivative vesicle delivery system and application thereof. Background The current prevention and treatment means for drug-induced deafness (such as caused by cisplatin) mainly comprise antioxidants (such as N-acetylcysteine), anti-inflammatory drugs, hormonal drugs (such as dexamethasone) and hearing protection agents (such as sodium thiosulfate). In addition, studies have been attempted to intervene with natural products such as resveratrol, tanshinone, etc., but they have poor targeting, low bioavailability, ambiguous mechanism of action, and limited clinical transformation. The prior improvement mainly focuses on improving the intra-cochlear distribution and residence time of drugs, such as drug delivery systems using liposome, nanoparticles and the like, but the problems of insufficient targeting, poor stability, complex preparation and the like are common. In the area of mechanistic studies, most studies remain only phenotypically observable, lacking systematic elucidation of signaling pathways. Disclosure of Invention Aiming at the defects of the prior art, the invention provides a curcumin-loaded targeting cell membrane derivative vesicle delivery system and application thereof. The aim of the invention can be achieved by the following technical scheme: In a first aspect the invention relates to a curcumin loaded targeted cell membrane derived vesicle delivery system comprising: Cell membrane vesicles; an IETP2 ear targeting polypeptide modified on the surface of the cell membrane vesicle; and curcumin encapsulated inside the cell membrane vesicles. Alternatively, the material of the cell membrane vesicles is derived from a cochlear hair cell line. Optionally, the curcumin exists in the cell membrane vesicle in a free form or in a form of being encapsulated in polymer nanoparticles, wherein the polymer nanoparticles are polylactic acid-glycolic acid copolymer nanoparticles. Alternatively, the IETP2 ear targeting polypeptide is immobilized on the cell membrane surface by means of covalent coupling, hydrophilic/lipophilic action or graft modification. More specifically, the IETP2 ear targeting polypeptide is grafted to Mal-PEG2k-DSPE phospholipid by a chemical modification method, and is modified on the surface of the cell membrane vesicle by two self-assembly methods. Optionally, the mass ratio of the IETP2 ear targeting polypeptide to the cell membrane material is from 1:20 to 1:200. In a second aspect, the invention relates to a method of preparing a delivery system comprising the steps of: extracting HEI-OC1 cell membrane, and preparing cell membrane vesicle by extrusion or ultrasonic method; grafting IETP2 polypeptide on Mal-PEG2k-DSPE phospholipid by a chemical modification method, and modifying the surface of the cell membrane vesicle by two self-assembly methods to obtain a targeting vesicle carrier; Curcumin is encapsulated in the targeting vesicle carrier by adopting a liposome extrusion method. In a third aspect, the invention relates to a pharmaceutical composition comprising the delivery system described above, and a pharmaceutically acceptable carrier, excipient or adjuvant. Optionally, at least one active ingredient selected from antioxidants, anti-inflammatory agents, hormonal agents or other hearing protection agents is also included, preferably, dexamethasone or N-acetylcysteine is included in the active ingredient. In a fourth aspect, the present invention relates to the use of a delivery system as described above or a pharmaceutical composition as described above for the preparation of a medicament for the prevention and treatment of deafness or hearing loss. Optionally, the deafness is aminoglycoside antibiotics, cisplatin chemotherapeutics or diuretics induced deafness; And the delivery system functions by activating cAMP/PKA/CREB signaling pathways, improving mitochondrial function, and inhibiting cochlear hair cell apoptosis. The invention has the beneficial effects that: 1) The targeting and the retention time of the cochlea of the curcumin are obviously improved; 2) At the same dose, the targeted delivery system can reduce hearing loss and hair cell injury caused by cisplatin more than free curcumin; 3) The system reveals the action mechanism of curcumin and provides clear theoretical basis for clinical development; 4) The delivery system has simple preparation process, good biocompatibility and better conversion prospect. Drawings The invention is further described below with reference to the accompanying drawings. FIG. 1 is a schematic diagram of the structure, preparation flow and mechanism of action of the targeted delivery system of the present application; FIG. 2 is a schematic diagram of the animal experiment design and grouping of the present