Construction of brain tumor-targeted drug delivery system based on multifunctional modified liposome

A brain tumor and liposome technology, applied in liposome delivery, pharmaceutical formulations, medical preparations of non-active ingredients, etc., can solve the problems of incomplete resection and poor curative effect

Inactive Publication Date: 2018-10-23
SUZHOU GENHOUSE PHARMA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment options for glioma are mainly surgery, radiotherapy and chemotherapy, but surgical treatment cannot be completely resected due to its an

Method used

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  • Construction of brain tumor-targeted drug delivery system based on multifunctional modified liposome
  • Construction of brain tumor-targeted drug delivery system based on multifunctional modified liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1. The targeting effect of the drug delivery system on tumor cells.

[0060] The U87 MG cells and HBL-100 cells in the logarithmic growth phase were digested with 2.5% trypsin, counted, and the cell concentration was 1×10 4 100 μL was inoculated in a 96-well plate, and there were blank group (unmodified liposome loaded with paclitaxel), control group (only AS1411 modified liposome loaded with paclitaxel) and experimental group (lipid modified with AS1411 and peptide modified plastid loaded with paclitaxel). The next day, the blank group, control group and experimental group were added with different drug-loading systems. After 48 hours, the cells were lysed and the paclitaxel content in the cells was detected by HPLC. It can be clearly found that the content of paclitaxel in tumor cells is significantly higher than that in normal cells HBL-100, which proves that targeting tumor cells is effective.

Embodiment 2

[0061] Example 2. The effect of the drug-carrying system on penetrating the blood-brain barrier.

[0062] Balb / C female mice (Shanghai Slack Animal Co., Ltd., clean grade).

[0063] The first group is the blank control group, and unmodified liposomes loaded with paclitaxel are injected into the tail vein;

[0064] The second group is the targeting glioma group, and only AS1411-modified liposomes loaded with paclitaxel are injected into the tail vein.

[0065] The third group is the blood-brain barrier group, with AS1411-modified and polypeptide-modified liposomes loaded with paclitaxel.

[0066] The mice were killed 48 hours after spraying the drug, and the brain tissue was taken out, and the content of paclitaxel was measured by HPLC. It was found that the content of paclitaxel in the brains of mice in the third group was significantly higher than that of the other two groups, indicating that the designed drug-loading system could penetrate the blood-brain barrier.

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Abstract

The invention designs a liposome vector, a surface modified polypeptide and a functional nucleic acid aptamer for loading of the drug paclitaxel so as to realize drug loading. Based on the advantage that the polypeptide can mediate crossing of a blood cerebral barrier, a functional nucleic acid molecule specifically recognizing glioma cells is targeted to glioma cells and then a liposome is fusedwith target cells, so targeted drug delivery is realized; and thus, the drug utilization rate is increased, and drug toxicity is reduced.

Description

technical field [0001] The present invention relates to penetrating the blood-brain barrier and targeting to glioma cells. Background technique [0002] Liposome is a spherical closed vesicle formed by phospholipids dispersed in water and encapsulating a part of the water phase. Phospholipids are arranged in an orderly manner by hydrophobic association to form a bilayer structure similar to biological membranes. There are different types of liposomes according to different classification methods. Liposomes are divided into small unilamellar liposomes and multi-lamellar liposomes according to the number of layers of the lipid bilayer they contain; Capsule liposomes; according to the charge, they can be divided into neutral liposomes, negatively charged liposomes and positively charged liposomes; according to their performance, they can be divided into general liposomes, pH sensitive liposomes, long-circulating liposomes, and magnetic liposomes Plastids, immunoliposomes, fle...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/26
CPCA61K9/127A61K47/26A61K47/42
Inventor 王奎锋周璐
Owner SUZHOU GENHOUSE PHARMA RES & DEV CO LTD
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