Camptothecin design and delivery approaches for elevating anti-topoisomerase I activities in vivo.
The camptothecins as a class have exhibited unique dynamics and reactivity in vivo, with respect to both drug hydrolysis and blood protein interactions. These factors have confounded their pharmaceutical development and clinical implementation. Recent bench and clinical research alike indicates that the combination of medicinal chemical and drug delivery approaches has been and will continue to be highly valuable in improving the overall therapeutic indices of camptothecin-based anti-topoisomerase I therapies. In the future the development of camptothecin analogues that exhibit highly specific human albumin interactions will likely be avoided, and agents such as the highly lipophilic DB-67 analogue with improved tissue stability will be evaluated. Drug delivery scientists will also devise better ways of targeting camptothecin therapies to solid tumors by using carriers such as tumor-targeted long-circulating liposomes.
Burke
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Medical Center, Lexington, Kentucky, USA. tgburke@pop.uky.edu
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D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D008081:Liposomes; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin