title: Factors affecting the size distribution of liposomes produced by freeze-thaw extrusion.
abstract: This paper describes the development of a protocol for the production of liposomes using a freeze-thaw extrusion methodology. Laser diffraction particle size analysis showed that the median diameter of freeze-thawed egg phosphatidylcholine multilamellar vesicles (eggPC MLVs) was increased when cholesterol was included in the bilayers. Using a freeze-thaw cycle of 3 min freezing in liquid nitrogen at -196 degrees C followed by 3 min thawing at 50 degrees C resulted in an anomalously large particle size for eggPC/cholesterol formulations. When liposomes were repeatedly freeze-thawed a maximum size was achieved after five freeze-thaw cycles. Dispersion of liposomes in sodium chloride solutions promoted size increases following freeze-thawing, suggesting that vesicles had aggregated or fused. Poloxamers P338 and P407 inhibited the size increases observed during freeze-thawing for eggPC MLVs dispersed in 1.0 M NaCl, probably through steric prevention of aggregation and fusion.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of London, Brunswick Square, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Castile
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005612:Freeze Drying; D005615:Freezing; D006358:Hot Temperature; D008081:Liposomes / Q000737:chemistry* / Q000187:drug effects; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D020442:Poloxamer / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D012996:Solutions
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D012996:Solutions; D020442:Poloxamer; D012965:Sodium Chloride; D002784:Cholesterol