The Fabrication Of Environmental Responsive Supramolecular Hydrogel And Drug Delivery

A series of thermo-responsive hydrogels based on Poly(N-isopropy-lacrylamide)(PNIPAM) were prepared as a carrier for the sustained drug release due to its unique physicochemical properties. However, the low response temperature, poor biocompatibility and the complexity of drug loading of those crosslinked hydrogel limited the application on human drug release performance and tissue engineering. To improve the situation, a novel thermo-sensitive supramolecular hydrogel based on self-assembly of a-cyclodextrin (α-CD) and gust copolymers was fabricated. The preparation and loading process of hydrogels were simple and convenient, and the response temperature could be achieved similar to body temperature by designing and controlling the topology structure of copolymers. Based on this, two guest copolymers containing PNIPAM and methoxypolyethylene glycols (MPEG) with different topological structures were synsethized to fabricate the thermo-responsive supramolecular hydrogel by host guest interactions between α-CD. The successful preparation of copolymers were certified by FT-IR,1H NMR; the supramolecular structures, gelation kinetics and response temperature were confirmed by differential scanning calorimeter (DSC), X-ray diffraction and rotational rheometer. The release kinetics studies were carried out to verify the feasibility on biological medicine sustained release, and the results were as follows:(1) A novel thermo-sensitive copolymer, Poly(NIPAM-co-MPEGM-A), was synthesized by free radical polymerization. Then, the supramolecular hydrogels were fabricated via inclusion complexation with a-CD and the copolymers in aqueous solutions. As the MPEG segments increased, the gelation time was decreased significantly. On the other way, the lower critical solution temperature (LCST) of hydrogel system rose by the increasing of PNIPAM. The hydrogels sustained period of12h at38℃with5-fluorocrail (5-Fu) as model drug.(2) The topological structures of copolymers were adjusted by reversible additive fragment transfer polymerization (RAFT) which containing two PNIPAM ends and MPEG segments in the middle. The triblock copolymers were then self-assembled with α-CD to form thermo-sensitive supramolecular hydrogels. The gelation kinetics study demonstrated that the gelation time of hydrogel system was gradually reduced with the increase of MPEG segments in block copolymer. The dynamic temperature scanning showed that two set of hydrogels had a response temperature closed to human body were prepared successfully. The drug release test in vitro of5-Fu shown the hydrogel could achieve a sustained release time above30h at38℃, which provided a potential application for drug delivery.