Pulmonary administration of resveratrol/hydroxypropyl-β-cyclodextrin inclusion complex: in vivo disposition and in vitro metabolic study

Until today, the clinical application of phytochemicals is still limited largely due to poor oral bioavailability. Pulmonary administration is considered as an attractive alternative to oral delivery as it can improve the pharmacokinetic properties of compounds with extensive metabolism. In this study, resveratrol was selected as a study model to evaluate the feasibility of pulmonary administration in the delivery of phytochemicals, aiming to promote their therapeutic potential. The pharmacokinetic investigation on resveratrol was conducted in rats. Compared with oral delivery, resveratrol in rats after pulmonary administration showed superior absorption and bioavailability (92.95%). Directed delivery of resveratrol to lungs also showed potential usefulness in the treatment of lung diseases as drugs rapidly accumulated in lung tissues and concentrations were more than 100 times those of oral delivery at early time points. The metabolic study was carried out using rat microsomes and showed that metabolic activity of lung was much lower than that of liver. The overall results indicate that pulmonary administration is an effective strategy for both systemic and local delivery of resveratrol.