SUSTAINED-RELEASE METHOTREXATE FOR INTRACAVITARY CHEMOTHERAPY

Methotrexate was encapsulated into a lipid-based drug-delivery system to create a slow-release formulation (Depo/methotrexate) for intracavitary administration. Depo/methotrexate was stable in storage at 4 degrees C for >4 months. In human plasma at 37 degrees C, the half-life of drug release was 40 days. After intraperitoneal injection of Depo/methotrexate in mice, the intraperitoneal apparent half-life of free methotrexate was 39.6 h, in contrast to a half-life of 0.5 h for the unencapsulated standard methotrexate (std/methotrexate). In L1210 murine leukemia model, the potency of a single dose of Depo/methotrexate was 334-fold higher, the increased life-span (ILS) was P-fold greater, and the therapeutic index was 2-fold higher than a single dose of std/methotrexate.