Preparation and Characterization of Nanoparticles Using Poly(N-isopropylacrylamide)- Poly(epsilon-caprolactone) and Poly(ethylene glycol)-Poly(epsilon-caprolactone) Block Copolymers with Thermosensitive Function

摘要

Thermosensitive nanoparticles were prepared via the self-assembly of two different poly(epsilon-caprolac-tone)-based block copolymers of poly(N-isopropylacrylamide)-b-poly(epsilon-caprolactone) (PNPCL) and poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using ~1H-NMR, turbidimetry, differential scanning microcalorimetry (micro-DSC), dynamic light scattering (DLS), and fluorescence spectroscopy. The copolymer mixtures (mixed nanoparticles, M1-M5, with different PNPCL content) formed nano-sized self-aggregates in an aqueous environment via the intra- and/ or intermolecular association of hydrophobic PCL chains. The microscopic investigation of the mixed nanoparticles showed that the critical aggregation concentration (cac), the partition equilibrium constants (K_v) of pyrene, and the aggregation number of PCL chains per one hydrophobic microdomain varied in accordance with the compositions of the mixed nanoparticles. Furthermore, the PNPCL harboring mixed nanoparticles evidenced phase transition behavior, originated by coil to the globule transition of PNiPAAm block upon heating, thereby resulting in the turbidity change, endothermic heat exchange, and particle size reduction upon heating. The drug release tests showed that the formation of the thermosensitive hydrogel layer enhanced the sustained drug release patterns by functioning as an additional diffusion barrier.