Prolonging
tumor exposure to
topoisomerase I inhibitors has been correlated to enhance the efficacy of those agents.
Lurtotecan, a water-soluble
camptothecin analog, was formulated as a liposomal
drug, NX211, to enhance the delivery of
drug to
tumors.
Tumor-bearing mice were treated with either [14C]NX211 containing [14C]
lurtotecan, [3H]NX211 containing [3H]
phosphatidylcholine or [14C]
lurtotecan, euthanized at selected times post-injection, and tissues, plasma, urine and feces were collected. These studies demonstrated that KB
tumors of [14C]NX211-treated mice had approximately 70-fold greater concentrations of [14C]
lurtotecan at 24 h, respectively, compared to concentrations of [14C]
lurtotecan of the KB
tumors of [14C]
lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of [14C]
lurtotecan for the KB
tumors of [14C]NX211-treated animals was over 17-fold greater than the AUC of [14C]
lurtotecan for the
tumors of [14C]
lurtotecan-treated animals. Treatment with [3H]NX211 demonstrated that the
lipid component continually accumulated over 24 h in the tissues. HPLC analysis of extracted material from
tumors of [14C]NX211-treated mice showed that more than 95% of the radioactive material was intact [14C]
lurtotecan. These findings are one of the keys justifying the development of a liposomal formulation of
lurtotecan, which has the intent to increase
tumor exposure and increase antitumor efficacy.