Preparation of Thermo-Responsive and Injectable Hydrogels Based on Hyaluronic Acid and Poly(N-isopropylacrylamide) and Their Drug Release Behaviors

摘要

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications.Semi-telechelic PNIPA Am,with amino groups at the end of each main chain,was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent,and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry.The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30-33 deg C.As the graft yield of PNIPAAm onto the HA backbone increased,the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition.The short chain PNIPAAm-grafted HA (M_w = 6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA (M_w= 13,100).PNIPAAm-grafted HA exhibited an increase in viscosity above 35 deg C,thus allowing the gels to maintain their shape for 24 h after in vivo administration.From the in vitro riboflavin release study,the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased.In addition,BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit,followed by a sustained release profile after 60 h.