An innovative biocompatible and degradable in situ hydrogel that can form rapidly under physiological condition by Michael type addition reaction between vinyl sulfone modified hyaluronic acid (HA-VS) and thiolated hyaluronic acid (HA-SH) or dextran (Dextran-SH) has been reported in previous study. In this project, this in situ forming hydrogel system is proposed to function as drug delivery device and provide sustained release of therapeutic for eye disease treatment. Polymer precursors of different molecular weight and degree of modification (DM) have been synthesized to obtain hydrogel of varied characteristics in gelation time, mesh size, and swelling ratio. Model protein PROTEIN V which has anti-angiogenesis effect was encapsulated in the hydrogel. Formulation of the hydrog...[ Read more ]

An innovative biocompatible and degradable in situ hydrogel that can form rapidly under physiological condition by Michael type addition reaction between vinyl sulfone modified hyaluronic acid (HA-VS) and thiolated hyaluronic acid (HA-SH) or dextran (Dextran-SH) has been reported in previous study. In this project, this in situ forming hydrogel system is proposed to function as drug delivery device and provide sustained release of therapeutic for eye disease treatment. Polymer precursors of different molecular weight and degree of modification (DM) have been synthesized to obtain hydrogel of varied characteristics in gelation time, mesh size, and swelling ratio. Model protein PROTEIN V which has anti-angiogenesis effect was encapsulated in the hydrogel. Formulation of the hydrogel was optimized to achieve sustained release of PROTEIN V up to 3 months. The release profile showed two phases: the initial burst within the first day followed by slow and sustained release with constant release rate, which indicates that the process is diffusion driven. The integrity of long-term released protein was demonstrated using Western-Blot technique. The PROTEIN V combined with hydrogel system was applied on retinal neovascularization animal model and showed significant therapeutic effect comparing to control group. Our findings suggest that the in situ hydrogel is a drug delivery device that can be administrated by intravitreal injection and provide sustained release of small protein therapeutic in eye disease treatment.