title: Hexosomes formed from glycerate surfactants--formulation as a colloidal carrier for irinotecan.
abstract: A new class of amphiphiles with a glycerate headgroup, recently shown to form reverse hexagonal phase in excess water, have been dispersed to form Hexosome dispersions comprising sub-200 nm particles retaining the internal nanostructure of the parent H(II) phase. The application of these novel materials to the development of a new injectable formulation of irinotecan was investigated. The formulation of irinotecan with a small percentage of oleic acid in oleyl glycerate permitted a clinically relevant dose of irinotecan to be dissolved in the glycerate surfactant and dispersed in aqueous medium to form an injectable particle-based dose form of irinotecan. Importantly, incorporation of irinotecan into Hexosomes at neutral pH did not result in conversion from the active lactone to the inactive carboxylate form on storage, and is hence a promising alternative to the current low pH formulation of irinotecan required to inhibit this conversion. Although release of irinotecan from the Hexosomes was shown to be virtually instantaneous from the Hexosomes on substantial dilution, the retention of the drug in lactone form at neutral pH demonstrates a potential application of these novel nanostructured particles in injectable drug delivery.
authors.affiliation: Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Pde, Parkville, Vic. 3052, Australia. ben.boyd@vcp.monash.edu.au
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.forename: Darryl V
authors.initials: DV
authors.lastname: Whittaker
authors.forename: Shui-Mei
authors.initials: SM
authors.lastname: Khoo
authors.forename: Greg
authors.initials: G
authors.lastname: Davey
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003102:Colloids; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004356:Drug Storage; D005988:Glyceric Acids / Q000737:chemistry*; D000077146:Irinotecan; D009994:Osmolar Concentration; D010316:Particle Size; D020442:Poloxamer; D012995:Solubility; D013012:Sorbitol; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003102:Colloids; D004337:Drug Carriers; D005988:Glyceric Acids; D013501:Surface-Active Agents; D014867:Water; D020442:Poloxamer; D013012:Sorbitol; D000077146:Irinotecan; D002166:Camptothecin