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.
MeSH terms
-
Animals
-
Antineoplastic Agents / administration & dosage*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacokinetics*
-
Camptothecin / administration & dosage*
-
Camptothecin / analogs & derivatives
-
Camptothecin / chemistry
-
Camptothecin / pharmacokinetics*
-
Carboxylic Acids / chemistry
-
Carboxylic Acids / pharmacokinetics
-
Chemistry, Pharmaceutical
-
Colonic Neoplasms / drug therapy
-
Colonic Neoplasms / metabolism
-
Delayed-Action Preparations
-
Drug Stability
-
Humans
-
Lactones / chemistry
-
Lactones / pharmacokinetics
-
Liposomes
-
Mammary Neoplasms, Experimental / drug therapy
-
Mammary Neoplasms, Experimental / metabolism
-
Mice
-
Mice, Nude
-
Rats
-
Rats, Sprague-Dawley
-
Solubility
-
Tissue Distribution
-
Xenograft Model Antitumor Assays
Substances
-
Antineoplastic Agents
-
Carboxylic Acids
-
Delayed-Action Preparations
-
Lactones
-
Liposomes
-
rubitecan
-
Camptothecin