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Method for controlled release of active small molecules based on liposomes and application thereof

A small molecule, liposome technology, applied in liposome delivery, prosthesis, pharmaceutical formulations, etc., can solve the problem of less research, and achieve the effects of simple raw materials, good induction and differentiation effect, and prolonged action time

Inactive Publication Date: 2019-10-15
PEKING UNIV SCHOOL OF STOMATOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In addition, there is a need for multifunctional surface modification of biomedical implant materials, but there are few studies in this area

Method used

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  • Method for controlled release of active small molecules based on liposomes and application thereof
  • Method for controlled release of active small molecules based on liposomes and application thereof
  • Method for controlled release of active small molecules based on liposomes and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] The preparation of embodiment 1 Aspirin liposome (Asp@Lipo)

[0098] 1.1 Preparation of Aspirin liposomes (Asp@Lipo)

[0099] The liposome-loaded aspirin was prepared by film dispersion method.

[0100] Take a round-bottomed flask, dissolve aspirin and lipids in a mixture of methanol and chloroform (1:1, v / v), predetermine the proportion of aspirin in the mixture of methanol and chloroform, and then mix it in different mixing volumes Proportional to add aspirin. Next, methanol and chloroform were removed using a rotary vacuum evaporator, followed by hydration of the lipid film with phosphate buffered saline (PBS). The aspirin-loaded liposomes can be obtained after ultrasonication in a water bath for 5 minutes (T=47° C.). It was sequentially passed through porous polycarbonate membranes (Millipore, USA) with pore diameters of 450 nm, 220 nm and 100 nm, each extruded 5 times to ensure the uniformity of the finally obtained liposome size. Then, the aspirin-loaded l...

Embodiment 2

[0177] Example 2 Construction of Aspirin / BFP-1 two-factor composite PS system

[0178] Preparation and characterization of different ratios of Aspirin / BFP-1 modified culture plate surface (PS-Asp@Lipo / BFP-1)

[0179] First, prepare Asp@Lipo according to the experimental method of 1.1 in Example 1.

[0180] Using dopamine technology, we grafted Asp@Lipo and BFP-1 polypeptides on PS culture plates according to the preset ratio Asp@Lipo:BFP-1=7:3, 5:5, 3:7.

[0181] The main experimental steps are as follows: firstly, 2 mL of dopamine solution (pH=8.5, 2 mg / mL) was added to each well of the culture plate, and then incubated on a constant temperature shaker (37° C., 70 rpm) for 24 hours. After washing twice with PBS, add 2 mL of activation solution (5 mM NHS, 2 mM EDC dissolved in 0.1 M MES buffer) to each well at room temperature to pretreat the polydopamine (PDA)-modified surface, activate for 40 min, discard the activation solution, and Asp@Lipo and BFP-1 polypeptides wer...

Embodiment 3

[0220] The preparation of the PS surface of embodiment 3 Dex / Mino liposome modification

[0221] 3.1.1 Dex / Mino liposome preparation

[0222] Prepared by thin film dispersion method; accurately weigh appropriate amount of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol), distearoyl Put phosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000-NH2) and Dex in an eggplant-shaped flask, add a mixed solvent of methanol and chloroform (1:1, v / v), shake to dissolve the solute; use rotary evaporation Drying machine (75rpm) in a constant temperature water bath (47°C) reduced pressure and dried thoroughly to remove the organic solvent, and a uniform lipid film was formed on the inner wall of the bottle; take an appropriate amount of hydration solution (a mixture of 120mM anhydrous sodium acetate and anhydrous calcium chloride) solution, pH=7.9) into an eggplant-shaped bottle, and ultrasonically hydrate in a constant temperature water bath (47°C) until the lipid mem...

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Abstract

The invention discloses a method for controlled release of active small molecules based on liposomes and an application thereof. The liposomes wrapped with the active small molecules are prepared by afilm dispersion method, and the method includes the following steps: (1) dissolving the active small molecules and lipids in a mixture of methanol and chloroform (1:1, v / v); (2) removing methanol andchloroform by a rotary vacuum evaporation instrument, and then hydrating a lipid membrane with a hydrating liquid; carrying out water bath ultrasonic treatment to obtain liposomes wrapped with the active small molecules, and extruding by a porous polycarbonate membrane; and dialyzing overnight; (3) adding a dopamine solution to a biomaterial, and gently shaking overnight evenly; and carrying outultrasonic cleaning in sterile distilled water; and (4) adding the liposomes loaded with the active small molecules, and carrying out static reaction; and then washing with a sterile phosphate buffersolution, and thus obtaining the surface of a culture plate modified by the liposomes with the small active molecules. In the method, the active small molecule liposomes are covalently grafted on thesurface of polystyrene, and the liposomes are used as a drug delivery carrier to realize controlled release of drugs.

Description

technical field [0001] The invention relates to a liposome-based active small molecule controlled release method and application thereof, belonging to the technical fields of drug controlled release and biomaterials. Background technique [0002] The liposome is structurally self-sealing, and can contain water-soluble and fat-soluble substances respectively or simultaneously (fat-soluble molecules are entrapped in the middle of the liposome bilayer membrane, and water-soluble molecules are entrapped in the innermost part of the liposome), and can Prevents drug degradation and is therefore widely used to control drug loading, delivery, and release. Currently, there are four main types of liposome drug delivery systems, including traditional liposomes, sterically stabilized liposomes, ligand-targeted liposomes, and therapeutic liposomes. As a well-established carrier for protecting and delivering drugs, free liposomes have been widely used to deliver drugs to pathological sit...

Claims

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Application Information

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IPC IPC(8): A61L27/54A61L27/50
CPCA61L27/50A61L27/54A61L2300/21A61L2300/41A61L2300/412A61L2300/414A61L2300/43A61L2300/602A61L2300/626A61L2400/18A61L2430/02
Inventor 魏世成许晓李艳
Owner PEKING UNIV SCHOOL OF STOMATOLOGY
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