A novel formulation of cyclosporine A/phosphatidylserine-containing liposome using remote loading method: Potential product for immunosuppressive effects

Abstract

In this study, two PEGylated and non-PEGylated liposomal formulations of Cyclosporine A (CsA) were prepared by remote loading procedure to improve the tissue distribution profile of CsA and the therapeutic efficacy thereof. DOPE/DOPS/Chol/α-Tocopherol/mPEG2000 (35/40/19.5/0.5/5) and DOPE/DOPS/Chol/α-Tocopherol (40/40/19.5/0.5) were examined in terms of their physicochemical stability, immunosuppressive efficiency, and pharmacokinetic profiles. Besides, the delayed-type hypersensitivity reaction (DTH) was studied from sheep red blood cells (SRBC) injection to male Wistar rats and skin allograft rejection transplanted from male C57BL into BALB/c mouse. Both liposomes had a size of about 162.2 ± 75 nm with a polydispersity index of <0.14, exhibited a high drug encapsulation efficacy (49.9–61.3%), and showed a long-term (6 months) shelf-life stability. Moreover, the liposomes enhanced the delivery of CsA and the improved immunosuppressive efficiency in vitro compared to non-liposomal CsA. In the animal studies, the liposomes also enhanced the drug half-life in the serum of the rat and improved the tissue distribution of CsA compared to non-liposomal CsA. Besides, the liposomes minimized the DTH and delayed the skin allograft rejection up to 17 days compared to CsA. To sum up, the liposomal formulations of CsA improved both the delivery profile and therapeutic efficacy of CsA. However, further studies need to be done to translate this formulation into the clinics.