Cyclodextrin nanosponge based hydrogel for the transdermal co-delivery of curcumin and resveratrol: Development, optimization, in vitro and ex vivo evaluation

The present study aims at the design of the transdermal co-delivery of curcumin (CUR) and resveratrol (RES) using cyclodextrin nanosponge based hydrogel. Cyclodextrin-based nanosponges (CDNS) were prepared by crosslinking cyclodextrin using pyromellitic dianhydride, loaded with curcumin and resveratrol, characterized and studied for synergism against breast cancer cells by in vitro cytotoxicity test. The nanosponges enhanced the in-vitro release of curcumin to 10 folds and resveratrol release to 2.5 folds compared to plain curcumin and resveratrol. CUR-CDNS and RES-CDNS combination showed a synergistic cytotoxic effect on MCF-7 cells with a combination index value of 0.29. A hydrogel base using carbomer and propylene glycol was developed to incorporate CUR-CDNS and RES-CDNS. The formulation was optimized for CUR, RES flux and gel property using 3-factor 3-level Box-Behnken design. The optimized hydrogel formulation was evaluated for physicochemical, photostability study, in vitro and ex vivo permeation study. Photostability of curcumin and resveratrol in CDNS-hydrogel formulation was increased to almost 5 and 7 folds respectively compared to hydrogel formulated without CDNS. The permeation of curcumin and resveratrol were significantly enhanced when delivered using CDNS-hydrogel base. The present work proposes the use of cyclodextrin nanosponge based hydrogel as an effective transdermal delivery system for curcumin and resveratrol co-delivery.