sirolimus and dioleoyl-phosphatidylethanolamine

Fusogenic liposomes are unique delivery vehicles capable of introducing their contents directly and efficiently into the cytoplasm.. 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.. 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.. 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.. Our results indicated that fusogenic liposomes can be useful carriers for improving the inhibition of T-cell proliferation.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cell Proliferation; Cells, Cultured; Chemistry, Pharmaceutical; Cholesterol; Drug Liberation; Drug Stability; Humans; Immunosuppressive Agents; Liposomes; Particle Size; Phosphatidylethanolamines; Sirolimus; T-Lymphocytes

Liposomes are increasingly employed to deliver chemotherapeutic agents, antisense oligonucleotides, and genes to various therapeutic targets.. The present investigation evaluates the ability of fusogenic pH-sensitive liposomes of rapamycin in increasing its antiproliferative effect on human breast adenocarcinoma (MCF-7) cell line.. Cholesterol (Chol) and dipalmitoylphosphatidylcholine (DPPC) (DPPC:Chol, 7:3) were used to prepare conventional rapamycin liposomes by a modified ethanol injection method. Dioleoylphosphatidylethanolamine (DOPE) was used to produce fusogenic and pH-sensitive properties in liposomes simultaneously (DPPC:Chol:DOPE, 7:3:4.2). The prepared liposomes were characterized by their size, zeta potential, encapsulation efficiency percent (EE%), and chemical stability during 6 months. The antiproliferative effects of both types of rapamycin liposomes (10, 25, and 50 nmol/L) with optimized formulations were assessed on MCF-7 cells, as cancerous cells, and human umbilical vein endothelial cells (HUVEC), as healthy cells, employing the diphenyltetrazolium bromide (MTT) assay for 72 h.. The particle size, zeta potential, and EE% of the liposomes were 165 ± 12.3 and 178 ± 15.4 nm, -39.6 ± 1.3, and -41.2 ± 2.1 mV as well as 76.9 ± 2.6 and 76.9 ± 2.6% in conventional and fusogenic pH-sensitive liposomes, respectively. Physicochemical stability results indicated that both liposome types were relatively stable at 4 °C than 25 °C. In vitro antiproliferative evaluation showed that fusogenic pH-sensitive liposomes had better antiproliferative effects on MCF-7 cells compared to the conventional liposomes. Conversely, fusogenic pH-sensitive liposomes had less cytotoxicity on HUVEC cell line.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Antibiotics, Antineoplastic; Cell Proliferation; Cholesterol; Dose-Response Relationship, Drug; Drug Stability; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Liposomes; MCF-7 Cells; Particle Size; Phosphatidylethanolamines; Sirolimus; Surface Properties