In vitro evaluation of liposomal cyclosporine

Abstract

The commercially available intravenous formulation of cyclosporine (CSA) is associated with acute hemodynamic changes, resulting in significant renal dysfunction. The present study investigated the properties of two liposomal CSA formulations: dimyristoylphosphatidylcholine (DMPC): stearylamine 7:1 (A) and DMPC: dimyristoylphosphatidylglycerol (DMPG) 4:1 molar ratio (B) developed as an alternative for the i.v. CSA. The optimal drug: lipid weight ratio was 1:20 for both formulations. The liposomal suspensions were obtained by rehydrating the lyophilized powder containing CSA and the lipids with saline. CSA entrapment was 90–95% for both formulations. The encapsulation efficiency of the lyophilized powder stored at 2–5°C was 95% at 24 h and not significantly different with either formulation. The encapsulation efficiency of liposomal formulations A and B in saline was 99 ± 1 and 50 ± 1%, respectively, after 5 days. In 50% serum, the encapsulation efficiency measured as percentage drug remaining entrapped at different time points was 90 ± 3 and 53 ± 4% for A and B, respectively, at 24 h. In vitro activity of both liposomal formulations demonstrated greater potency compared to the commercially available CSA i.v. formulation (A, 69.3 ± 14.8%; B, 50.8 ± 11.5%; i.v., 27.4 ± 20.6% inhibition of T-lymphocyte proliferation; p < 0.05 at 10 −3 mM). The present study shows that liposomes can be used as a drug delivery system for CSA and result in an enhanced in vitro immunosuppressive potency compared with the i.v. formulation.