Colorectal cancer (CRC) is the second leading cause of death in the United States in the adult population. When detected at early stages, the survival rate is higher than 70% but when diagnosed at a metastatic stage, the 5-year survival rate significantly declines to 15%. In recent years, immunotherapy has shown promising results in a selective patient population with advanced or metastatic CRC with microsatellite instability (MSI) and mismatch repair (MMR). Hydrogels are a growing field of research to improve the delivery of monoclonal antibodies. In this work, a gellan gum-based (GG) hydrogel noncovalently cross-linked using trilysine (TLA) was characterized for its drug release and diffusion properties. A partial release of the checkpoint inhibitor anti-programmed death-1 (aPD-1) was observed with an almost 40% cumulative release within the first 24 h. FRAP analysis showed varying diffusion rates (μm2/s) for Atto 488-IgG (2.63 ± 0.32), 60-76 kDa FITC-Dextran (2.65 ± 0.31), and 150 kDa FITC-Dextran (2.80 ± 0.83), with a 70-90% recovery postbleaching. Additionally, intratumoral delivery of aPD-1 was evaluated in a CRC mouse (C57BL/6) tumor model inoculated with MC38 cells. Quantification of aPD-1 in the plasma and tumor showed an increase in concentration by 1.5- and 3-fold, respectively, when delivered using the intratumoral hydrogel route in comparison with either intraperitoneal (i.p.) or drug-free intratumoral administration. Overall, this noncytotoxic hydrogel provided an alternative delivery route for aPD-1, maximizing its presence both in circulating blood and in the treatment site, serving as a simple localized delivery system in CRC.
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