Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly(N-isopropylacrylamide) and adamantyl-poly(ethylene glycol).

Chemotherapy is facing several limitations such as low water solubility of anticancer drugs and multidrug resistance (MDR) in cancer cells. To overcome these limitations, a thermoresponsive micellar drug delivery system formed by a non-covalently connected supramolecular block polymer was developed. The system is based on the host-guest interaction between a well-defined β-cyclodextrin (β-CD) based poly(N-isopropylacrylamide) star host polymer and an adamantyl-containing poly(ethylene glycol) (Ad-PEG) guest polymer. The structures of the host and guest polymers were characterized by 1H and 13C NMR, GPC and FTIR. Subsequently, they formed a pseudo-block copolymer via inclusion complexation between β-CD core and adamantyl-moiety, which was confirmed by 2D NMR. The thermoresponsive micellization of the copolymer was investigated by UV-vis spectroscopy, DLS and TEM. At 37°C, the copolymer at a concentration of 0.2mg/mL in PBS formed micelles with a hydrodynamic diameter of ca. 282nm. The anticancer drug, doxorubicin (DOX), was successfully loaded into the core of the micelles with a loading level of 6% and loading efficiency of 17%. The blank polymer micelles showed good biocompatibility in cell cytotoxicity studies. Moreover, the DOX-loaded micelles demonstrated superior therapeutic effects in AT3B-1-N (MDR-) and AT3B-1 (MDR+) cell lines as compared to free DOX control, overcoming MDR in cancer cells.