Controlled protein release from in situ hydroge
We are developing a novel in situ hydrogel system for the prolonged release of protein therapeutics in the eye, aiming to reduce the frequency of injection from once per month to at most once every 3 to 6 months. “In situ gel” is a liquid that becomes solidified to a gel quickly after injection. Inside the eye, the hydrogel acts as a protective network so that the drug encapsulated inside can be released slowly to maintain therapeutic concentration for a long time.
The in situ hydrogel are prepared from modified polysaccharides that form chemical crosslinks under physiological conditions. We developed a facile method to graft vinylsulfone (VS) and thiol (SH) onto the polymers, which then form crosslinks by a efficient “click” reaction. We demonstrated the applicability of the reaction scheme to a wide variety of polymers, including hyaluronic acid, dextran, PVA, PEG and alginate, and the ease of controlling the degree of modification.
We applied the blob theory to the formulation of hydrogel for controlled release of protein. Using this model, we developed a depot for releasing the anti-angiogenic antibody, bevacizumab, for multiple months. The in situ hydrogel formation, found to be biocompatible in animal studies, was able to maintain the antibody concentration above therapeutic concentration in rabbit eye for at least 6 months.