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Polymer nanocarrier capable of promoting endocytosis and cell nucleus targeting and preparation method of polymer nanocarrier

A nanocarrier and polymer technology, which is applied in the directions of non-active components of polymer compounds, medical preparations with non-active components, and medical preparations containing active components, etc. , to improve the effect of tumor treatment, ensure safety and stability, and reduce the effects of toxic and side effects

Inactive Publication Date: 2017-05-10
SOUTHWEST JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A ligand-modified drug carrier can only target a certain type of tumor, but cannot overcome a variety of cancers, which greatly limits its clinical application

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0024] 1) Preparation of N,N'-carbonyldiimidazole-activated polyethylene glycol: Weigh 10 grams of polyethylene glycol with a molecular weight of 2000 and dissolve it in 100 mL of dry dichloromethane, N,N'-carbonyldiimidazole ( CDI) 0.9 g was dissolved in 3 mL of dry dichloromethane, and was added dropwise into a solution of polyethylene glycol in dichloromethane with a separatory funnel, and reacted at 25° C. for 6 hours under nitrogen protection. After the reaction, dichloromethane was removed by rotary evaporation, and the remaining concentrated solution was precipitated with 250 mL of glacial ether, filtered by suction, and dried in vacuum to obtain N,N'-carbonyldiimidazole-activated polyethylene glycol.

[0025] 2), Formation of amphiphilic copolymer: Take 9.5 grams of polyethylene glycol activated by N,N'-carbonyldiimidazole, 13.7 grams of caprolactone monomer and 0.137 grams of stannous octoate in a 150mL round bottom flask, vacuumize After 6 hours, react at 150° C. for...

example 2

[0032] In this example, the dimethyl maleic anhydride in Example 1 is replaced by succinyl chloride, and 40 mg of Tat-modified polymers are dispersed in 40 mL of pH 8.5 phosphate buffered saline solution, cooled to 0°C and stirred for one hour, and added to 20 drops of succinyl chloride were added dropwise thereto, and stirring was continued for 24 hours. After the reaction was completed, dialyzed with phosphate buffered saline solution of pH 7.4 for three days, and then freeze-dried to obtain the product. Other methods were the same as in Example 1.

example 3

[0034] In this example, the anticancer drug doxorubicin in Example 1 was replaced by hydroxycamptothecin. Other methods were the same as in Example 1, and hydroxycamptothecin nanoparticles were obtained, with a particle size of 112.4 nanometers.

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Abstract

The invention discloses a polymer nanocarrier capable of promoting endocytosis and cell nucleus targeting and a preparation method of the polymer nanocarrier. The polymer nanocarrier material is an amphipathic block polymer, a hydrophobic end is a polyester capable of being biologically degraded and absorbed, a hydrophilic chain segment is polyethylene glycol with a terminal linked with polypeptide capable of promoting endocytosis and cell nucleus targeting, the polypeptide is modified by a small molecule, and an amido bond, linked with the polypeptide, of the small molecule responds to a faintly acid environment of tumors, so that the endocytosis and the nucleus targeting drug delivery are promoted; and a cell nucleus can be targeted by virtue of a cell nucleus targeting signal. The polymer nanocarrier material and medicines can form medicine-carrying nanoparticles in water through self-assembling, and the preparation method is simple.

Description

technical field [0001] The invention belongs to the technical field of drug controlled release, and more specifically relates to a polymer nanocarrier capable of improving cell endocytosis and cell nucleus targeting, and also relates to a preparation method of a polymer drug-loaded nanoparticle prepared by using the carrier material. Background technique [0002] Cancer has a high morbidity and mortality rate worldwide, and chemotherapy is currently the most important means of treating cancer. The toxic and side effects of anticancer drugs seriously limit their clinical application. In order to overcome this obstacle, many researchers often use nanoparticles such as liposomes and polymer micelles as drug carriers. The main basis for this application is that polymer micelles carry anticancer drugs into cells through endocytosis, avoiding a large number of drug molecules dispersed in the systemic circulation and absorbed by normal tissues, resulting in systemic toxicity. Dru...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/42A61K31/704A61K31/4745A61K33/24A61P35/00
CPCA61K9/5153A61K9/5169A61K31/4745A61K31/704A61K33/24
Inventor 周绍兵敬雨亭熊翔明阳郭星赵静雅
Owner SOUTHWEST JIAOTONG UNIV
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