Development of transdermal based hydrogel formulations of vinorelbine with an evaluation of their in vitro profiles and activity against melanoma cells and in silico prediction of drug absorption

Abstract The primary course of melanoma treatment involves surgery in association with chemotherapy. One potential agent is vinorelbine (VNR). While it displays anti-proliferative activity against melanoma cell lines, it presents a low oral bioavailability and intravenous administration often causes irritation, phlebitis and pain at the injection site. The aim of this study was to develop Pluronic® F-127 (PF-127) hydrogels containing VNR for the transdermal route of administration. Hydrogels composed of either 15% (G15), 20% (G20), 23% (G23) or 25% (G25) PF-127 aqueous solutions were loaded with a VNR propylene glycol solution. Their release and permeation profiles for VNR were evaluated in a Franz diffusion cell. In addition, their rheological behavior, visual aspect during storage and the in silico prediction of VNR absorption using GastroPlus® were evaluated. The G20 and G23 formulations showed similar release and permeation profiles with the G20 demonstrating a higher permeation of VNR at 8h (p