Preparing method of drug-loaded liposome

A technology of liposomes and blank liposomes, which is applied in the direction of liposome delivery, can solve the problems of high encapsulation efficiency drug loading and low encapsulation efficiency drug loading, so as to improve drug loading and increase The encapsulation efficiency of liposomes for most drugs and the effect of a wide range of drug loading

Inactive Publication Date: 2020-08-18
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to solve the problem of low encapsulation efficiency of drug liposomes in the prior art, especially the low drug loading capacity, and provide a new method for liposome drug loading. The present invention can effectively load different types of drugs into lipids. Plastids, and the encapsulation efficiency, especially the drug loading is high

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 Negatively charged PEGylated liposomes loaded with non-dissociated drug curcumin

[0026] Use 0.9% NaCl aqueous solution (adjust pH=9 with hydrochloric acid) as the water phase, use SPC / DPPG / DPPE-PEG2000 (12:2:1, molar ratio) as the film-forming material, and adopt film dispersion-hydration-extrusion method Prepare blank liposomes (total lipid concentration is 10%), then add curcumin, drug / phospholipid (1:5, w / w), heat up to 50°C and stir (300rpm) for 5h, cool and control the temperature at 2°C , continue stirring for 3h; repeat the high temperature-low temperature cycle operation 0, 1, 3 times to obtain curcumin liposomes.

[0027] Before and after drug loading, the average particle diameter detected by DLS was 150nm, PDI=0.30, ζ=8mV. Remove free drug with Sephadex G50 chromatographic column, detect content by HLPC, cycle high temperature-low temperature operation 0, 1, 3 times, encapsulation efficiency is respectively 20%, 37%, 53%; drug loading (drug / lipid...

Embodiment 2

[0028] Example 2 Neutral PEGylated liposome-loaded amphoteric drug topotecan hydrochloride

[0029] With pH 7.4 phosphate buffer as the aqueous phase and DSPC / CHO / DPPE-PEG2000 (12:7:1, molar ratio) as the membrane material, blank liposomes were prepared by ethanol injection (the total lipid concentration was 2 %), then add topotecan hydrochloride, drug / phospholipid (1:10, w / w), heat up to 70°C and stir (20rpm) for 0.5h, cool and control the temperature at 4°C, continue stirring for 1h; repeat high temperature- The low-temperature cycle operation was performed 3, 5, and 7 times to obtain topotecan hydrochloride liposomes.

[0030] Before and after drug loading, the average particle diameter detected by DLS was 120 nanometers, PDI=0.21, ζ=2mV. Sephadex G50 chromatographic column was used to remove free drug, HLPC detected the content, cycled high temperature-low temperature operation for 3, 5, and 7 times, the encapsulation efficiency was 52%, 85%, and 97% respectively; the dru...

Embodiment 3

[0031] Example 3 Positively charged PEGylated liposomes loaded with baicalein

[0032] With pH 2.5 phosphate buffer as the aqueous phase and DSPC / DPPE-PEG2000 / DOTAP (15:5:1, moleratio) as the membrane material, blank liposomes (liposomes) were prepared by film dispersion-hydration-ultrasonic The concentration is 5%), then add baicalein, drug / phospholipid (1:20, w / w), heat up to 80°C and stir (80rpm) for 2h, cool and control the temperature at 10°C, continue stirring for 4h; repeat high temperature- Low-temperature cycle operation was performed 5, 7, and 9 times to obtain baicalein liposomes respectively.

[0033] Before and after drug loading, the average particle size detected by DLS was 120 nanometers, PDI was about 0.21, ζ=39mV, free drug was removed by Sephadex G50 chromatographic column, content was detected by HLPC, cycle high temperature-low temperature operation 5, 7, 9 Times, encapsulation efficiency were 41%, 59%, 76%; drug loading were 2.1%, 2.95%, 3.8%. It shows ...

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PUM

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Abstract

The invention relates to a liposome drug loading method, and belongs to the technical field of pharmaceutical preparations. The preparing method comprises the steps: preparing a blank liposome, mixinga to-be-encapsulated drug with the blank liposome, raising the temperature, stirring for a certain period of time, then cooling, continuously stirring for a certain period of time, and repeating thehigh-temperature-low-temperature cycle operation for multiple times to obtain the drug-loaded liposome. The liposome drug loading method provided by the invention is wide in application range and relatively high in encapsulation efficiency, especially drug loading capacity.

Description

technical field [0001] The invention relates to a liposome drug loading method, which belongs to the technical field of pharmaceutical preparations. Background technique [0002] Liposome is a single or multilayered microcapsule composed of ordered lipid bilayers. Liposome belongs to the colloidal system, has a cell-like structure, has a strong affinity with the cell membrane, and can increase the ability of the encapsulated drug to penetrate the cell membrane. Liposomes have good biocompatibility, can realize targeted delivery of drugs in vivo, and have many advantages such as prolonging drug action time, increasing drug stability in vivo and in vitro, reducing drug toxicity, and enhancing pharmacological effects. [0003] At present, liposome preparation methods are mainly based on phospholipid dispersion technology, which can be classified into the following three categories: (1) based on solvent or co-solvent dispersion technology, for example, thin film dispersion meth...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K9/127
CPCA61K9/1277A61K9/1278
Inventor王汀王宁
OwnerANHUI MEDICAL UNIV