Synthesis of star block, thermosensitive poly(L-lactide)-star block-poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide) copolymers and their self-assembled micelles for controlled release

A series of star block copolymers poly(L-lactide)-star block-poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide) (PLLA-sb-P(NIPAAm-co-HMAAm)) with different molar feed ratios of NIPAAm and HMAAm were designed and synthesized. An ideal P(NIPAAm-co-HMAAm) (13: 1) copolymer was found, which exhibited reversible phase transitions at around 36.8 degrees C, being close to human physiologic temperature (37 degrees C). Such a star block copolymer was comprised of a hydrophobic PLLA arm and an average of six hydrophilic P(NIPAAm-co-HMAAm) arms, determined by molecular weight analysis. The amphiphilic PLLA-sb-P(NIPAAm-co-HMAAm) copolymer was capable of self-assembling into nanosized micelles in water, and transmission electron microscopy images showed that the self-assembled nanoparticles were regularly spherical in shape. The anticancer drug methotrexate (MTX) was loaded in the polymeric micelles, and the in vitro release behavior of MTX was investigated. It was found that resulting PLLA-sb-P(NIPAAm-co-HMAAm) micelles showed a drastic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of the micellar shell structure.