title: Formulation and in vitro characterization of thermosensitive liposomes for the delivery of irinotecan.
abstract: The effect of the lipid composition on the physicochemical properties of a liposomal carrier containing irinotecan (CPT-11) and its in vitro antitumoral activity on a colon cancer cell line has been investigated. The paper describes the procurement of a novel and easy-to-prepare temperature-sensitive carrier for CPT-11 and proves its suitability as delivery system on the basis of its ability to incorporate the drug and on its efficiency to promote drug internalization. Permeability data, studied in vitro in a simulated biological medium at different temperatures, showed that both the nature of the lipids and the ratio in which they have been mixed play a key role in the release of the encapsulated product. Stable temperature-sensitive liposomes with good drug incorporation efficiency were obtained and characterized. The cellular uptake and the cytotoxic activity of the CPT-11 liposomal formulation were compared with those corresponding to the free drug with promising results, being concentration and time dependent and significantly higher. Thus, it could be interpreted that the greatest cytotoxic effect of liposomal CPT-11 was because of the increased uptake provided by the liposomal carrier. Studies of cell cycle and annexin V binding showed drug-induced changes in cell cycle dynamics and the proapoptotic effect of liposomal CPT-11.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, 08028, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Casadó
authors.forename: Maria Lluïsa
authors.initials: ML
authors.lastname: Sagristá
authors.forename: Margarita
authors.initials: M
authors.lastname: Mora
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D018938:Caco-2 Cells; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D008081:Liposomes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D000077146:Irinotecan; D002166:Camptothecin
keywords: Caco-2 cells; Irinotecan; Liposomes; controlled release; cytotoxic activity; drug delivery; drug uptake; responsive delivery systems