Preparation method of temperature and pH sensitive shell cross-linked polymeric micelle

Abstract

The invention relates to a preparation method of a temperature and pH sensitive shell cross-linked polymeric micelle, characterized by synthesizing a temperature and pH sensitive diblock copolymer by reversible addition-fragmentation chain transfer (RAFT) polymerization, and then using small-molecule dialdehyde or diacid to carry out part crosslinking on the shell structure of a self-assembled polymeric micelle. The method has the characteristics of simpleness, convenience, high preparation yield, no environmental pollution, and the like. The prepared diblock copolymer has the advantages of strong functionality and narrow molecular weight distribution. By using small-molecule cross-linking agent to carry out part crosslinking on the micelle shell structure, under the precondition of guaranteeing the stability of the polymeric micelle, the preparation method has the characteristics of strong feasibility and simple operation, and can reutilize micelles, etc. The obtained temperature and pH sensitive shell cross-linked polymeric micelle has excellent drug loading performance, can rapidly and efficiently adsorb readily degradable or indissoluble drugs under different concentration conditions, is a new generation high performance drug loaded product, and can be applied in the medicine fields of in vivo transfer, gene vectors, and the like.

Description

technical field [0001] The invention belongs to the technical field of chemical engineering and new materials, and in particular relates to a preparation method of temperature- and pH-sensitive shell cross-linked polymer micelles. Background technique [0002] Polymer micelles are self-assembled by polymers in solvents. Because of their excellent tissue permeability, good compatibilization effect, and structural diversity, they have become one of the hot research topics at home and abroad. However, the poor stability of polymer micelles limits its practical application to a large extent, especially in the process of micellar self-assembly, when the polymer concentration is lower than the critical micelle concentration, the dilution effect of micelles affects controlled release efficiency. In order to improve the stability of polymer micelles and the integrity of supramolecular nanostructures so that they can be better applied in biological environments, people have been wor...

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Problems solved by technology

[0003] Chinese patent CN03105348.3 has reported a kind of synthetic method of methylpolyethylene glycol-polyester block copolymer polymicelle, and it makes the ratio of methylpolyethylene glycol and polyester less than 50:50, and this block Segmented copolymer micelles have a lower critical micelle concentration, but this kind of micelles has strict requirements on the proportion of polymer blocks and low stability, which will inevitably affect the performance of the product and limit the application

Chinese patent CN200510137409.9 reports a method for forming shell cross-linked polymer micelles. First, the terminal of the amphoteric polymer is functionalized, and then a plurality of amphoteric polymers containing cross-linkable functional groups are aggregated to form polymer micelles. And the cross-linkable functional group is located in the outer layer of the polymer micelle. The design of the shell cross-linked polymer micelle is simple, but the formation process requires a high solvent, the size of the micelle is not uniform, and the operability is not strong, which also limits its further use.

Chinese patent CN201010115227.2 reports a preparation method of shell cross-linked polymer micelles with metal nanoparticles as cross-linking agent. This method forms polymer micelles through self-assembly of amphiphilic polymers containing reactive functional groups , and make the reactive functional groups on the shell surface of the polymer micelles, then add metal nanoparticles, and use the metal nanoparticles to chemically combine with the reactive functional groups to form a metal nanoparticle cross-linked polymer Micelles, the polymer micelles have good biocompatibility, but due to the use of metal nanoparticles cross-linked, it is limited in practical applications such as clinical medicine

At present, there are no public literature reports and reports about the partial crosslinking of the shell structure of temperature-sensitive polymer micelles by small molecule crosslinkers at home and abroad, and the temperature-sensitive shell crosslinked polymer micelles are also pH-sensitive. patent application

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