Targeted liposome drug delivery system and preparation method and application thereof

A technology targeting liposomes and delivery systems, applied in liposome delivery, drug delivery, drug combination, etc., can solve the problems of low drug efficacy, high toxicity and side effects, etc.

Active Publication Date: 2021-11-02
BEIJING CHILDRENS HOSPITAL AFFILIATED TO CAPITAL MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problems of low drug efficacy and high toxic side effects of traditional sclerotherapy for lymphatic malformations, the present invention proposes a liposome drug delivery system for the sclerotherapy of lymphatic malformations for the first time

Method used

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  • Targeted liposome drug delivery system and preparation method and application thereof
  • Targeted liposome drug delivery system and preparation method and application thereof
  • Targeted liposome drug delivery system and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0039] S1: Weigh 30 mg of HA (M=8000), swell it in 10 mL distilled water, dissolve it ultrasonically, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 60 mg and N-hydroxysulfosuccinimide (NHS) 90 mg, add sodium hydroxide solution to adjust the pH value to 7.5, activate in a water bath at 37°C for 24 h, add dropwise 72 mg DSPE-PEG-NH 2 The suspension was reacted overnight, and the excess reactants and by-products in the reaction solution were removed by dialysis using a dialysis membrane with a pore size of 5000 to prepare DSPE-PEG-HA;

[0040]S2: Weigh 120 mg of lecithin (Spc), 30 mg of cholesterol (Cho), and 6 mg of bleomycin into a single-necked bottle, add 10 mL of chloroform solvent, ultrasonically dissolve it fully, and place the solvent in a rotary evaporator. Evaporate, add 3 mL (pH=7.4) of PBS buffer solution and 2 ml of DSPE-PEG-HA in PBS solution (2 mg / mL), hydrate in a water bath at 60 °C for 1 h, and ultrasonicate the suspension with a probe; ...

Embodiment 2

[0042] The preparation materials and method are the same as those in Example 1, the difference is only in the liposome extrusion process, specifically, the suspension after ultrasonic treatment of the probe is sequentially extruded 20 times through 450nm and 200nm polycarbonate membranes respectively to obtain HA- BLM-lip NPs.

Embodiment 3

[0044] The preparation materials and method are the same as in Example 1, the difference is only in the liposome extrusion process, specifically, the suspension after the ultrasonic treatment of the probe is sequentially extruded 20 times through the polycarbonate membranes of 450nm, 200nm and 100nm respectively to obtain HA-BLM-lipNPs.

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Abstract

The invention discloses a targeted liposome drug delivery system, the drug delivery system is composed of a targeting ligand modified liposome entrapped hardener, and the targeting ligand is hyaluronic acid. The hardener used in the invention is a water-soluble small molecule drug, and the liposome membrane material is prepared from lecithin, cholesterol and distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeting ligand in a mass ratio of (30-32): (7-9): 1. The liposome has a phospholipid bilayer, is self-closed in structure, can entrap a hardener inside the liposome, has good stability, and can prevent water-soluble drugs from being rapidly degraded and reduce the release speed of the drugs. In addition, hyaluronic acid is used for modifying the drug-loaded liposome, so targeted transportation of the drug in lymphangial malformation pathological tissues can be realized.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a targeted liposome nano-medicine delivery system, which can be used for targeted sustained-release treatment of lymphatic malformations. Background technique [0002] Lymphatic malformation is a congenital developmental malformation of the lymphatic system. Lesions can compress important parts such as the airway and esophagus, seriously affecting the health and quality of life of patients. For lymphatic malformations, the current first-line clinical treatment is sclerotherapy, which has the advantages of safe operation and wide application range. However, simple local injection of sclerosing agents such as bleomycin has a short residence time in the lesion and a low effective utilization rate; if the injection dose is increased, serious side effects such as pulmonary fibrosis will be caused. In addition, general anesthesia is required before sclerotherapy ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K9/127A61K38/14A61K45/00A61K47/24A61K47/28A61K47/69A61P43/00
CPCA61K47/61A61K47/6911A61K9/1271A61K47/24A61K47/28A61K45/00A61K38/14A61P43/00
Inventor 张欣倪鑫邰隽王生才侯毅张雪溪史继云李小达马晓途陈俊李晓丹郭永丽张杰
Owner BEIJING CHILDRENS HOSPITAL AFFILIATED TO CAPITAL MEDICAL UNIV
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