Macromolecular Research, Vol.14, No.1, 87-93, February, 2006
Preparation of Thermo-Responsive and Injectable Hydrogels Based on Hyaluronic Acid and Poly(N-isopropylacrylamide) and Their Drug Release Behaviors
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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 PNIPAAm, 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 ℃. 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 (Mw =6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA (Mw= 13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35 ℃, 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.
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