7-t-Butyldimethylsilyl-10-Hydroxycamptothecin (DB-67) Precipitation in the Presence of Ferrous Ions: A Liposomal Delivery Strategy

7-t-butyldimethylsilyl-10-hydroxycamptothecin (DB-67/AR-67), a drug that exhibits anti-cancer activity, is currently in clinical development for the treatment of solid tumors. The clinical efficacy of DB-67 may be improved by targeting its delivery to solid tumors. Liposomal encapsulation is a promising formulation approach to improve the delivery of chemotherapeutic agents to tumor sites. However, formulation strategies for liposomal loading and retention of hydrophobic drugs such as the neutral camptothecin DB-67 have had limited success. Therefore, complexation and/or salt formation of DB-67 with iron ions are explored as a potential loading and retention strategy. The extent of drug precipitation due to potential formation of Fe2+-DB-67 salts was investigated at suspension conditions of pH = 7.8, [DB-67]=100 µg/mL, and [Fe2+] = 0 and 0.001M. At one hour after suspension formation, the DB-67 concentration in the supernatant was analyzed by HPLC.In the suspension with iron ions, 52.60% of DB-67 was found in the precipitate whereas the sample without the presence of iron ions had 4.55% of DB-67 in the precipitate. Results suggest that Fe2+ cations may significantly affect the degree of precipitation of DB-67 carboxylate. Future studies will be attempted to load Fe2+-DB-67 salt in liposomes and explore its effect on drug release.