a k + Responsive amphiphilic block copolymer drug-loaded micelles and preparation method thereof

Abstract

A kind of K in the present invention + The responsive amphiphilic block copolymer drug-loaded micelle is composed of an amphiphilic block copolymer and a hydrophobic drug embedded in a hydrophobic inner core formed by the amphiphilic block copolymer. The preparation method of the drug-loaded micelles: (1) dissolving the block copolymer and the hydrophobic drug in the co-solvent of the block copolymer and the hydrophobic drug to prepare a solution; (2) heating the gained solution to high At the low critical dissolution temperature of the block copolymer, deionized water or distilled water is added dropwise to the solution under stirring to obtain a mixed solution with a concentration of the amphiphilic block copolymer of 0.1-2 mg / ml. After the drug-loaded micelle is released in vivo, its amphiphilic block copolymer can be excreted through normal metabolic pathways, so as to avoid potential toxicity caused by accumulation in the body.

Description

technical field [0001] The invention belongs to the field of stimuli-responsive micelles, in particular to a new K + Responsive amphiphilic block copolymer drug-loaded micelle and its preparation method. Background technique [0002] Block copolymer micelles are a new drug nanocarrier developed rapidly in recent years. In aqueous solution, the hydrophobic block in the amphiphilic block copolymer constitutes the core, and the hydrophilic block constitutes the shell, forming a block copolymer micelle with a spherical core-shell structure. Block copolymer micelles have the following advantages as drug carriers: (1) The critical micelle concentration (CMC) is low, with a high degree of thermodynamic and kinetic stability, and it is not easily destroyed even below the CMC, and has high resistance to dilution ability; (2) self-assemble in aqueous solution to form micelles, the inner core can be loaded with hydrophobic drugs, and the hydrophilic surface makes it difficult to be r...

AI Technical Summary

Problems solved by technology

However, this K + Responsive block copolymer micelles still have certain deficiencies and defects: first, the structure of the block copolymer itself is relatively complex, and there are many synthesis steps, and it is necessary to introduce a hydrophilic substance such as acrylamide to adjust the molecular weight of the entire block copolymer. Low critical solution temperature (LSCT), and the adjustment process is relatively cumbersome; second, the low critical solution temperature (LCST) of the block copolymer in the drug-loaded micelles outside the cell is above the physiological temperature of 37 ° C, and the micelles maintain the original form, while entering the cell in response to K + Finally, the LCST of the block copolymer migrates to low temperature. Under the physiological temperature of 37°C, the hydrophilic end of the block copolymer changes from a swelling state to a shrinking state, and the micellar structure dissociates, making the entire block copolymer Shrinks into a compact micelle-like structure, which becomes larger in size after agglomeration in the body, and is difficult to be cleared by the kidneys, and accumulation in the body may cause potential toxicity; the third is that the drug-loaded micelle responds to K + Finally, the entire block copolymer shrinks into a tightly hydrophobic colloidal shape, and this agglomerated colloidal structure will wrap certain hydrophobic drugs and reduce the drug utilization rate.

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