Hydrogels for combination delivery of antineoplastic agents

The systemic delivery of anticancer agents has been widely investigated dur ing the past decade but localized delivery may offer a safer and more effec tive delivery approach. We have designed and synthesized a novel hydrogel t o locally deliver antineoplastic agents, and demonstrate the different type s of release that can be achieved from these hydrogels using three model dr ugs: methotroxate, doxorubicin, and mitoxantrone. Alginate was chemically m odified into low molecular weight oligomers and crosslinked with a biodegra dable spacer (adipic dihydrazide) to form biodegradable hydrogels. The mode l antineoplastic agents were loaded into the hydrogel via three different m echanisms. Methotrexate was incorporated within the pores of the hydrogel a nd was released by diffusion into the surrounding medium. Doxorubicin was c ovalently attached to the polymer backbone via a hydrolytically labile link er and was released following the chemical hydrolysis of the linker. Mitoxa ntrone was ionically complexed. to the polymer and was released after the d issociation of this complex. These three release mechanisms could potential ly be used to deliver a wide selection of antineoplastic agents, based on t heir chemical structure. This novel delivery system allows for the release of single or combinations of antineoplastic agents, and may find utility in localized antineoplastic agent delivery. (C) 2001 Elsevier Science Ltd. Al l rights reserved.