Paclitaxel-loaded cyclodextrin-cored unimolecular micelles and their in vivo behavior

摘要

Polymeric drug delivery systems for major diseases have experienced considerable development in the past decades due to the versatility of polymer chemistry. However, self-assembled micelles from multi-macromolecules suffer from poor stability and imprecise architecture. Unimolecular micelles have many unique advantages, including high stability, accurate architecture and high drug loading. Herein, a series of well-defined, unimolecular, star-shaped, polymers (beta-CD-s-PAA-PTX), with beta-cyclodextrin as a core, poly(acrylic acid) (PAA) as branches, and the anticancer drug paclitaxel covalently linked to the branches, were synthesized. The pCD-s-PAA-PTX can form unimolecular micelles in aqueous solutions, which was attributed to their amphiphilic structure. Drug loading increased with the increase of the molecular weight of the star-shaped polymer beta-CD-spolyacrylic acid (beta-CD-s-PAA), and the maximum drug loading reached 59 wt%. The fate of the unimolecular micelles with different molecular weights in tumor-bearing mice was investigated. Unimolecular micelles with low molecular weights could not effectively accumulate in tumors, while high-molecular weight unimolecular micelles tended to accumulate in tumor sites. This study provided the effect of the molecular weights of the beta-CD-cored unimolecular micelles on their in vivo behavior.