title: Accumulation of vinblastine into transfersomes and liposomes in response to a transmembrane ammonium sulfate gradient and their cytotoxic/cytostatic activity in vitro.
abstract: Vinblastine was encapsulated into liposomes composed from lipids dimiristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC), with cholesterol and transfersomes with sodium cholate prepared by the thin film hydration method. The percentage of vinblastine encapsulation, the stability of transfersomes and liposomes and the rate of release of encapsulated vinblastine at 37 degrees C were studied. The results showed that encapsulation of vinblastine into liposomes was higher than 98% at a drug/phospholipid molar ratio from 0.17 to 0.18, while encapsulation of vinblastine into transfersomes varied from 50% to 80% at a drug/phospholipid molar ratio from 0.05 to 0.09. The retention of drug in liposomes and in transfersomes was found to be time/dependent. The retention of drug in transfersomes compared to the liposomes was reduced due to the presence of sodium cholate which caused destabilization and reduced the main phase transition temperature Tm of the PC bilayers. The cytotoxic/cytostatic activity of the two liposome formulations and the two transfersome formulations with or without encapsulated vinblastine were examined against nine human cell lines and the parameters GI50, TGI, LC50 were estimated according to the NCI protocol. Free DPPC/sodium cholate liposomes found to exhibit strong antiproliferative activity in contrast to the other three free liposomal formulations (DPPC/cholesterol, DMPC/cholesterol, DMPC/sodium cholate). On the other hand, vinblastine encapsulated into the liposomes found to exhibit 20-fold less activity on average, in the three parameters calculate compare to the free vinblastine.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Technology, Panepistimiopolis, Zografou, University of Athens, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Maswadeh
authors.forename: C
authors.initials: C
authors.lastname: Demetzos
authors.forename: K
authors.initials: K
authors.lastname: Dimas
authors.forename: S
authors.initials: S
authors.lastname: Hatziantoniou
authors.forename: A
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: M
authors.initials: M
authors.lastname: Rallis
authors.forename: P
authors.initials: P
authors.lastname: Dallas
authors.forename: G
authors.initials: G
authors.lastname: Papaioannou
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000645:Ammonium Sulfate / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004339:Drug Compounding; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D020358:Sodium Cholate / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D014747:Vinblastine; D002784:Cholesterol; D020358:Sodium Cholate; D000645:Ammonium Sulfate; D004134:Dimyristoylphosphatidylcholine