Cationic liposomes mediated transdermal delivery of meloxicam and ketoprofen: Optimization of the composition, in vitro and in vivo assessment of efficiency

New liposomes modified with pyrrolidinium surfactants containing a hydroxyethyl fragment (CnPB, n = 12, 14, 16) were prepared for transdermal delivery of non-steroidal anti-inflammatory drugs. In order to obtain the optimal composition, the surfactant/lipid molar ratio (0.02/1; 0.029/1; 0.04/1) and the amphiphile hydrocarbon tail length were varied. Rhodamine B was loaded in all formulations, while meloxicam and ketoprofen in selected ones. For liposomes studied the hydrodynamic diameter was in the range of 80-130 nm, the zeta potential ranged from +35 to +50 mV, EE was 75-99%. Liposome modification leads to a prolonged release of the rhodamine B (up to 10-12 h) and faster release of non-steroidal drugs (up to 7-8 h) in vitro. The ability to cross the skin barrier using Franz cells was investigated for liposomal meloxicam and ketoprofen. The total amount of meloxicam and ketoprofen passed through the Strat-M (R) membranes during 51 h was 51-114 mu g/cm(2) and 87-105 mu g/cm(2) respectively. The evaluation of transdermal diffusion ex vivo showed that total amount of liposomal ketoprofen passed through the skin during 51 h was 140-162 mu g/cm(2). Liposomes modified with C16PB were found as the most effective inflammation reducing formulation in the carrageenan edema model of rat paw.