Thermosensitive chitosan hydrogel for implantable drug delivery: Blending PVA to mitigate body response and promote bioavailability

摘要

Thermosensitive hydrogels promise to be the injectable implants for long-term controlled drug release; however, body response to the implanted hydrogels and its unpredictable impacts on drug release complicates their applications. In the present study, hydrophilic polymer poly(vinyl alcohol) (PVA) was blended into the thermosensitive hydrogel composed of chitosan and glycerophosphate to mitigate the body responses and promote the drug bioavailability. The effects of PVA on the surface properties of the hydrogel were evaluated by zeta-potential, water contact angle, and cell attachment. Body responses were explored by histological examination via subcutaneously implanting the hydrogels into Sprague-Dawley rats. Drug release in vivo and bioavailability were determined with cyclosporine A (CsA) employed as the model drug. The results showed that, on one hand, the presence of PVA improved the surface hydrophilicity of the hydrogel and inhibited the cell attachment on the hydrogel, which alleviated the further cell infiltration and tissue integration in body; and on the other hand, blending of PVA led to the more rapid gel formation and more compact network, which resisted the dehydration and survived the hydrogel from cell division. These advantages benefited the controlled release and absorption of CsA, and contributed to the higher drug bioavailability.