title: Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors.
abstract: Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar in a mouse xenograft tumor model.
authors.affiliation: ImaRx Therapeutics, Inc., 1635 E. 18th St, Tucson, AZ 85719, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Williams
authors.forename: Rachael
authors.initials: R
authors.lastname: Lansdown
authors.forename: Robert
authors.initials: R
authors.lastname: Sweitzer
authors.forename: Marek
authors.initials: M
authors.lastname: Romanowski
authors.forename: Rachel
authors.initials: R
authors.lastname: LaBell
authors.forename: Rajan
authors.initials: R
authors.lastname: Ramaswami
authors.forename: Evan
authors.initials: E
authors.lastname: Unger
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019073:HT29 Cells; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D000077146:Irinotecan; D007783:Lactones / Q000737:chemistry; D008027:Light; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D009368:Neoplasm Transplantation; D010316:Particle Size; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000737:chemistry; D059003:Topoisomerase Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007783:Lactones; D012709:Serum Albumin; D059003:Topoisomerase Inhibitors; D000077146:Irinotecan; D002166:Camptothecin