title: pH-sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules.
abstract: Negatively charged liposomes are endocytosed by the coated vesicle system and accumulate in acidic intracellular vesicles. Liposomes that become unstable at acidic pH improve cytoplasmic delivery of membrane-impermeant macromolecules such as calcein (CAL) and FITC dextran (18 or 40 kDa). Oleic acid (OA): phosphatidylethanolamine (PE) (3:7 mole ratio) liposomes become permeable to CAL at pH less than 7.0. Control liposomes of phosphatidylserine:PE or OA:phosphatidylcholine are stable at pH 4-8. OA:PE liposomes promote cytoplasmic delivery of encapsulated CAL to CV-1 cells, as evidenced by the emergence of diffuse, cytoplasmic CAL fluorescence. Delivery requires metabolic energy and is partially inhibited by chloroquine or monensin, which raise the pH of intracellular vesicles.
authors.forename: R M
authors.initials: RM
authors.lastname: Straubinger
authors.forename: N
authors.initials: N
authors.lastname: Düzgünes
authors.forename: D
authors.initials: D
authors.lastname: Papahadjopoulos
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003911:Dextrans; D004355:Drug Stability; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007668:Kidney; D007700:Kinetics; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines
chemical_list: D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; C007740:fluorexon