Multicompartment hydrogels for the local delivery of chemotherapic drugs

Over 85% of human cancers are solid tumors. The effectiveness of anticancer therapy in solid tumors depends on adequate delivery of the therapeutic agent to tumor cells. Inadequate delivery would result in residual tumor cells, which in turn would lead to regrowth of tumors and possibly development of resistant cells. The most prominent option, for now, is the local delivery of chemotherapic drugs into the cavity resection of the tumor. However, the burst release of massive concentrations of the drugs usually boosts the side effects of chemotherapy. Aiming to block the burst release a new drug delivery system (DDS) for the local delivery of Doxorubicin (DOX) was designed and tested, combining different materials and techniques. Following a bottom-up approach, porous spherical calcium carbonate (CaCO3) microspheres, with high loading properties, were loaded with DOX and Layer by Layer (LbL) assembled by biocompatible and biodegradable polyelectrolytes, dextran sodium sulfate (DSS) and polyarginine (PARG). Then, a protocol for the fabrication of alginate (Alg) hydrogels associated with LbL coated drug loaded CaCO3 microspheres were developed by combining internal and external gelation. Therefore, injectable multicompartment hydrogels (MCH) for the local and sustained delivery of chemotherapeutic drugs, with the ability to block the burst release, were developed and characterized.