Research On Thermosensitive Graft Copolymeric System For Drug Delivery

Poly (N-isopropylacrylamide) (PNIPAAm) was grafted to dextran using eerie ion as redox initiator. The graft copolymers formed temperature responsive materials and can be used to construct polymeric micelles as drug carriers for colon-site specifically delivery. The chemical structure of the graft copolymers was characterized by FTIR, 1H~ and 13C-NMR spectroscopy. The influence of reaction conditions on the grafting parameters was investigated. It was found that the percentage of homopolymer formation (H%), the grafting efficiency (GE%) and the grafting (G%) of the copolymers increased with increasing the amount of the eerie catalyst used. Extension of the duration of graft reaction increased GE% and G% of the copolymers, suggesting that G% of the copolymers could be readily manipulated by changing copolymerization duration. Higher grafting temperature was in favor of increasing GE% and G%, however, when the reaction temperature was above the LCST of the copolymers, GE% and G% decreased.Phase behavior of dextran-graft-poly (N-isopropylacrylamide) (PNIPAAm) polymers in aqueous solution are investigated using DSC and the optical transmittance of the copolymers in the aqueous solution by UV-Vis instrument. It is found that with the increase of grafting (G%) of the copolymers the endothermic enthalpy during the phase transition increases significantly and the transition temperature decreases slightly. The phase transition behavior of the copolymers is scanning rate dependent. It is proposed that by using this thermal responsive property of the copolymers, drugs could be incorporated into the micelles without employing any organic solvent.Since the stability of the polymeric micelles plays a crucial role in drug delivery, two techniques were employed to detect the critical micellization phenomenon of the copolymers: the surface tension measurement and the fluorescent probe technique with pyrene as a probe molecule. It was found that the critical micellar concentration (cmc) of the copolymers showed significant dependence on temperature. The cmc of the copolymers decreased with the increase of the grafting degree of the copolymers. The results of two methods revealed that when the temperature below the LCST of the copolymers, a classic one-break curve was also exhibited. This phenomenon might be related with the differences in the hydrophilicity between dextran and PNIPAAm. The results of dynamic light scattering measurement and atomic force microscopy indicated that the graft copolymers form micelles in a spherical morphology, and for the copolymer with the G% of 33.8% formed micelles in the mean diameter of less than 30 nm in aqueous solution. The AFM result shows clearly that the morphology of the constructed micelles at the temperature above the LCST of the copolymer is in spherical shape and the average size of the dried micelles is about 80 nm in diameter.The enzymatic degradation rate of the dextran-g-PNIPAAm copolymer was determined by measuring the release of reducing oligosaccharides, which are products of the degradation process. The result indicated that the degradation rate increased with tine dextranase concentration and G%. The drug release result indicated the dextran-g-PNIPAAm copolymers may have potential as colon-tageted drug release carriers.