A formulation consisting of camptothecin conjugated to a hydrophilic, cyclodextrin-based linear polymer with potential antineoplastic activity. Upon intravenous administration, camptothecin is slowly released from camptothecin-polymer conjugate IT-101 at the tumor site and taken up by tumor cells. During the S phase of the cell cycle, camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. Compared to camptothecin alone, this formulation exhibits a prolonged half life and improved biodistribution, enhancing tumor exposure while reducing systemic side effects. In addition, camptothecin-polymer conjugate IT-101 may overcome certain types of multidrug resistance (MDR).
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