Evaluation of Trilysine-Cross-Linked Gellan Gum for Intratumoral Delivery of Anti-PD‑1 in a Colorectal Cancer Mouse Tumor Model
Carolina Villarreal-Otalvaro, Francini Luna, Rosangel A. Ramos Espinoza, Eric D. Lombardini, Zephyr Paxton, Luis Vidali, Jeannine M. Coburn
TL;DR
This study evaluates a hydrogel for delivering anti-PD-1 therapy to colorectal cancer tumors in mice, showing improved drug retention and effectiveness.
Contribution
A noncytotoxic gellan gum-based hydrogel is proposed for localized delivery of anti-PD-1 in colorectal cancer.
Findings
The hydrogel showed a 40% cumulative release of aPD-1 within 24 hours.
Intratumoral delivery increased aPD-1 concentration in plasma and tumor by 1.5- and 3-fold compared to other routes.
FRAP analysis revealed varying diffusion rates for different molecular weights in the hydrogel.
Abstract
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…
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Taxonomy
TopicsPolysaccharides Composition and Applications · Advanced Drug Delivery Systems · Hydrogels: synthesis, properties, applications