Liposomal encapsulation increases the activity of the topoisomerase I inhibitor topotecan.

Topotecan, a topoisomerase I poison and water-soluble derivative of camptothecin, has shown promise in treating solid tumors; however, the drug is unstable under physiological conditions and converts to an inactive form within 30 minutes. Encapsulating topotecan in liposomes (LIP-TPT) minimizes inactivation. The efficacy of LIP-TPT was examined with a novel in vivo bioassay called ICE for In vivo Complexes of Enzyme. This bioassay uses antibodies to probe DNA for the presence of topoisomerase I covalent complexes and thereby allows direct quantification of topoisomerase I driven DNA adducts in living cells. We report that LIP-TPT was three- to fourfold more effective than free TPT in stabilizing covalent topoisomerase I-DNA intermediates inside tumor cells. These findings reveal that liposomal wrapping permitted effective delivery of camptothecin derivatives to active enzyme in the nucleus of the cell.