Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs

Layer-by-layer(LbL)-assembled polymeric films capable of differentially releasing dual anticancer drugs to achieve synergetic therapeutic effects were fabricated. Doxorubicin (DOX) was first conjugated to hyaluronic sodium(HA) via acid labile hydrazone bonds to produce HA-DOX prodrugs. Then HA-DOX was alternately deposited with 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC) to produce (HACC/HA-DOX)(n) (n is the number of deposition cycle) film. Methotrexate (MTX) was then loaded into (HACC/HA-DOX)(20) film by a post-diffusion process. MTX was quickly released due to the breakage of its electrostatic interaction with film component HACC. Meanwhile, DOX was released in a sustained manner because of the slow hydrolysis of hydrazine bonds. The synergetic therapeutic effects can be achieved by fast release of cell cycle specific drug MTX to effectively inhibit the proliferation of cancer cells and by sustained release of cell cycle non-specific drug DOX to kill cancer cells. The present study provides a new way for designing polymeric films for controlled release of multiple therapeutic agents.