title: Modified lactone/carboxylate salt equilibria in vivo by liposomal delivery of 9-nitro-camptothecin.
abstract: The lactone stability of camptothecins is critical for their anticancer activity. A stable liposomal 9-nitro-camptothecin formulation was developed to circumvent the drawbacks of low aqueous solubility and lactone instability and to provide sustained release of the agent in blood circulation. The potential merits of the formulation were demonstrated by its profoundly improved lactone stability in vivo, favorable pharmacokinetic and biodistribution characteristics in rats, and enhanced preclinical efficacy in tumor-bearing athymic mice.
authors.affiliation: College of Pharmacy, University of Houston, 1441 Moursund St., Texas Medical Center, Houston, TX 77030, USA. dchow@uh.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Chow
authors.forename: L
authors.initials: L
authors.lastname: Gong
authors.forename: M D
authors.initials: MD
authors.lastname: Wolfe
authors.forename: B C
authors.initials: BC
authors.lastname: Giovanella
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D002264:Carboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003692:Delayed-Action Preparations; D004355:Drug Stability; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D003692:Delayed-Action Preparations; D007783:Lactones; D008081:Liposomes; C079905:rubitecan; D002166:Camptothecin