title: Lactone stability and tissue distribution of free and liposomal encapsulated 9-nitrocamptothecin in rats following intravenous injection.
abstract: 9-Nitrocamptothecin (9-NC) is a newly developed but poorly soluble derivative of camptothecin (CPT), which has a wide spectrum of anticancer activity in preclinical evaluation. Lactone moiety is a key structural feature for the antitumor activity of CPT analogs including 9-NC. Lactone stability versus time profiles of 9-NC in vivo following intravenous (i.v.) administration of free and liposomal encapsulated 9-NC has been investigated in this article. After i.v. injection of 9-NC solution, it was found that lactone stability of 9-NC in liver was the poorest in vivo and even worse than that in plasma. In other tissues, lactone stability of 9-NC was better than that in plasma. After liposomal encapsulation, both lactone and total 9-NC concentrations in reticuloendothelial system (RES) tissues, for example, spleen, liver, and lung, were significantly increased. In particular, liposomal encapsulation had a significant improving effect on the lactone stability of 9-NC in the liver. The lactone percentage was increased from 39.11 +/- 16.93% to 65.57 +/- 9.73% (p < .05) at 10 min and from 30.99 +/- 6.54% to 51.22 +/- 11.10% (p < .01) at 30 min. On the basis of these results, a theoretical explanation of lactone stability in vivo was discussed. In summary, liposomal encapsulation, which resulted in passive targeting and a significant improvement of lactone stability in the liver, might have clinical utility.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
authors.forename: Minling
authors.initials: M
authors.lastname: Liu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007275:Injections, Intravenous; D007783:Lactones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; C079905:rubitecan; D002166:Camptothecin