THERMORESPONSIVE CYCLODEXTRIN-POLY(N-ISOPROPYLACRYLAMIDE) STAR POLYMER FOR ANTICANCER DRUG DELIVERY APPLICATIONS

Abstract

Currently, there are still several limitations in chemotherapy, such as poor water solubility of the anticancer drugs and multidrug resistance (MDR) in cancer cells. In this research, different thermoresponsive drug delivery systems based on poly(N-isopropylacrylamide) (PNIPAAm) and cyclodextrins (CDs) were developed to overcome these limitations. A well-defined PNIPAAm star host polymer with a β-CD core was synthesized via atom transfer radical polymerization (ATRP) method. Paclitaxel (PTX) was solubilized by inclusion complexation with the β-CD core. The thermoresponsive carrier exhibited enhanced cellular uptake and delivery of PTX at body temperature, overcoming MDR in AT3B-1 cancer cells. PNIPAAm star polymer was further used to complex with adamantyl-containing poly(ethylene glycol) (Ad-PEG), to form non-covalently connected micelles. Doxorubicin (DOX) was loaded into the thermoresponsive micelles and achieved superior in vitro cell cytotoxicity as compared to free DOX control, in both MDR+ and MDR- cancer cells. Moreover, an injectable polypseudorotaxane-based supramolecular hydrogel formed between α-CD and PEG chains of the thermoresponsive copolymer was developed. Enhanced rheological properties and sustained release of the hydrophobic drug, DOX, were achieved by the thermoresponsive hydrogel at body temperature. In addition, micelles released from the dissolved hydrogel could effectively deliver the encapsulated DOX to both MDR+ and MDR- cancer cells.