Thermosensitive t -PLA-b -PNIPAAm tri-armed star block copolymer nanoscale micelles for camptothecin drug release

Abstract

Thermosensitive polylactide-block-poly(N-isopropylacrylamide) (t-PLA-b-PNIPAAm) tri-armed star block copolymers were synthesized by atom transfer radical polymerization (ATRP) of monomer NIPAAm using t-PLA-Cl as macroinitiator. The synthesis of t-PLA-Cl was accomplished by esterification of star polylactides (t-PLA) with 2-chloropropionyl chloride using trimethylolpropane as a center molecule. FT-IR, 1H NMR, and GPC analyses confirmed that the t-PLA-b-PNIPAAm star block copolymers had well-defined structure and controlled molecular weights. The block copolymers could form core-shell micelle nanoparticles due to their hydrophilic-hydrophobic trait in aqueous media, and the critical micelle concentrations (CMC) were from 6.7 to 32.9 mg L−1, depending on the system composition. The as-prepared micelle nanoparticles showed reversible phase changes in transmittance with temperature: transparent below low critical solution temperature (LCST) and opaque above the LCST. Transmission electron microscopy (TEM) observations revealed that the micelle nanoparticles were spherical in shape with core-shell structure. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin-loaded copolymer micelles. Camptothecin drug release studies showed that the copolymer micelles exhibited thermo-triggered targeting drug release behavior, and thus had potential application values in drug controlled delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4429–4439