Abstract
To enhance the water solubility of α-cyclodextrin (CD) polyrotaxanes (PRs) and achieve effective drug loading, we polymerized 2-hydroxyethyl methacrylate and 2-tert-butoxy-N-(2-(methacryloyloxy)ethyl)-N,N-dimethyl-2-oxoethanaminium successively from a α-CD-PR-based macroinitiator by a two-step ATRP followed by cleaving the tert-butyl ester groups, providing a α-CD-PR-cored multiarm copolymer. The multiarm copolymer had reactive hydroxyl pendant groups in the inner block of the arms, which were used to incorporate antitumor agent paclitaxel (PTX). The outer block of the arms was zwitterionic poly(carboxybetaine) and had high hydrophilicity and zero net electric charge in a neutral environment. This feature endowed the PTX-loaded multiarm copolymer with high water solubility and prolonged blood circulation. The blood circulation half-life of the PTX-loaded multiarm copolymer was determined to be about 7.7 h versus 18.8 ± 1.5 min of the reported blood circulation half-life of the PTX injected as commercial Taxol. The PTX-loaded multiarm copolymer was proved to be efficient in tumor accumulation and suppression.
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