Fusogenic liposomal formulation of sirolimus: improvement of drug anti-proliferative effect on human T-cells.

CONTEXT Fusogenic liposomes are unique delivery vehicles capable of introducing their contents directly and efficiently into the cytoplasm. OBJECTIVE The objective of this study was to evaluate the potential of fusogenic liposomes containing Sirolimus to improve its anti-proliferative effect on T-lymphocyte cells. MATERIALS AND METHODS Conventional liposomes containing Sirolimus were prepared from Dipalmitoylphosphatidylcholine (DPPC) and cholesterol using the modified ethanol injection method. To prepare fusogenic liposomes, dioleoylphosphatidylethanolamine (DOPE) was added to the conventional liposome formulation. The liposomes were characterized by their size, zeta potential, encapsulation efficiency percent (EE%) and chemical stability during 6 months. The in vitro release of liposomes, anti-proliferative effect and liposome uptake of both types of liposomes with optimized formulations were studied on human T-lymphocyte cells employing the MTT assay and fluorescein isothiocyanate-loaded liposomes. RESULTS AND DISCUSSION The particle size of the liposomes was evaluated between 138 and 650 nm and mean zeta potential was in the range of -32.95 to -45.60 mV. The average EE% of the prepared conventional and fusogenic liposomes were 76.9% and 80.5%, respectively. Liposomal formulations released only 10-20% of encapsulated drug without any burst effect. In vitro immunosuppressive evaluation on T-cells showed that fusogenic liposomes have the best anti-proliferative effects and uptake on T-lymphocyte cell compared to the conventional liposomes. CONCLUSION Our results indicated that fusogenic liposomes can be useful carriers for improving the inhibition of T-cell proliferation.