title: Fusogenic pH sensitive liposomal formulation for rapamycin: improvement of antiproliferative effect.
abstract: BACKGROUND
  Liposomes are increasingly employed to deliver chemotherapeutic agents, antisense oligonucleotides, and genes to various therapeutic targets.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences , Tabriz , Iran .
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghanbarzadeh
authors.forename: Arash
authors.initials: A
authors.lastname: Khorrami
authors.forename: Leila
authors.initials: L
authors.lastname: Mohamed Khosroshahi
authors.forename: Sanam
authors.initials: S
authors.lastname: Arami
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002784:Cholesterol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D020123:Sirolimus / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; D020123:Sirolimus
keywords: Antiproliferative effect; breast cancer; fusogenic pH-sensitive liposome; rapamycin