Biodegradable Polymers for Application as Robust Immunomodulatory Biomaterial Carrier Systems

The field of immunotherapeutics is rapidly evolving with the advent of cell therapies, complex biologics, and a host of other compounds. Polymeric carriers are often used to tune the safety and efficacy profiles of these novel drugs. Despite their prevalence in pre-clinical and clinical applications, non-degradable materials present delivery challenges including diffusion-limited release, frustrated phagocytosis, and limited clearance. In contrast, biodegradable polymeric systems provide a safer alternative in addition to displaying advantageous properties for the delivery of immunotherapies. In this review, discussion of polymers including poly(lactic-co-glycolic acid) (PLGA), poly(beta-amino esters) (PBAEs), acetalated dextran (Ace-DEX), chitosan, alginate, and hyaluronic acid (HA) as immunomodulatory biomaterial carriers suggest that a variety of systems can be used to generate tailored formulations for different therapeutic payloads and disease indications. These carrier systems can enhance the delivery of immunotherapies via tunable degradation rates, enhanced antigen-presentation, and inherent immunomodulatory properties of the biomaterials, among other mechanisms. Polymers formulated for immunomodulatory applications can be synthetic, semi-synthetic, or naturally derived. Therefore, it is crucial to consider the environmental impact of polymer sources, particle fabrication methods, and solvent usage to sustainably develop effective immunomodulatory therapies in this evolving field.