Biodegradable and thermoresponsive micelles of triblock copolymers based on 2-(N,N-dimethylamino)ethyl methacrylate and epsilon-caprolactone for controlled drug delivery

Amphiphilic triblock copolymers, poly(2-(N,N-dimethylamino)ethyl methacrylate)(x)-block-poly(caprolactone)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate)(x), PDMAEMA(Co), were synthesized. Polymerization and structural features of the polymers were analyzed by different physicochemical techniques (GPC,H-1 NMR and FTIR). Formation of hydrophobic domains as cores of the micelles was studied by 1H NMR and further confirmed by fluorescence. Dynamic light scattering measurements showed a monodispersed size distribution only for the copolymer with the lowest degree of polymerization, while increasing the length of PDMAEMA blocks leads to a bimodal size distribution. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PDMAEMA at temperatures between 54 and 87 C. The triblock copolymer micelles were loaded with the sparingly water-soluble anticancer drug, chlorambucil, by a dialysis procedure. The drug release profile monitored by fluorescence showed that the release of chlorambucil from PDMAEMA nanoparticles is controlled by a combined degradation-diffusion mechanism. (c) 2008 Elsevier Ltd. All rights reserved