Carbonyl and carboxylate crosslinked cyclodextrin as a nanocarrier for resveratrol: in silico, in vitro and in vivo evaluation

Abstract

The purpose of the study was to explore the effect of different type of crosslinked cyclodextrins for the delivery of poorly soluble, photosensitive drug, resveratrol. Crosslinkers, diphenyl carbonate and pyromellitic dianhydride were used to prepare carbonyl (NS-I) and carboxylate (NS-II) crosslinked cyclodextrin respectively. The solubility and in silico molecular interaction of resveratrol with these NS at different crosslinker ratio were studied. The results showed enhanced solubility and better interaction of resveratrol with nanosponges prepared with 1:4 Cyclodextrin: crosslinker ratio. The drug-loaded nanosponges (RES-NS-I and II) prepared using 1:4 crosslinked NS-I and II were characterized using DSC, PXRD, SEM, FTIR and evaluated for particle size, zeta potential, photodegradation, in vitro drug release, in vitro cytotoxicity and in vivo oral bioavailability in rats. Physical characterization confirmed the molecular inclusion of drug with NS. The release of the drug was increased to 2.5–3 folds in the dissolution medium, with initial drug release faster with RES-NS-II. Photostability was enhanced to 2.3 fold with RES-NS-II. The cytotoxicity test exhibited 1.5 fold reduction in IC50 with drug-loaded NS. RES-NS-II exhibited 2.5 fold increase in Cmax and fourfold decrease in Tmax. Carboxylate crosslinked Cyclodextrin using pyromellitic dianhydride proves to be an effective nanocarrier for resveratrol.