Poly(lactic-co-glycolic acid) (PLGA)-based vaccine delivery systems for fish: physicochemical properties,...

Vaccination is widely regarded as the most effective strategy for controlling infectious diseases that compromise the sustainability and productivity of global aquaculture. Although inactivated and subunit vaccines are commonly applied, their protective efficacy often depends on potent adjuvants to induce robust and durable immune responses. In aquatic settings, environmental exposure and physiological barriers in fish-including enzymatic degradation, pH fluctuations, osmotic stress, and mucosal and integumentary defenses-pose substantial challenges to antigen stability and delivery efficiency. To address these constraints, advanced delivery systems have been developed to enhance antigen protection, facilitate transport to lymphoid tissues, and improve antigen presentation to immune cells. Among these, biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA)-based microparticles (MPs) and nanoparticles (NPs) have emerged as versatile and promising platforms. PLGA has been extensively utilized in human pharmaceutical applications and is increasingly being investigated for veterinary purposes, including fish vaccines. This review summarizes the physicochemical properties of PLGA, elucidates its controlled degradation behavior and antigen release kinetics, and examines PLGA particle-mediated antigen uptake, processing, and presentation mechanisms that contribute to immune activation in teleost fish. Recent advances in PLGA-based vaccines targeting major aquatic pathogens are also discussed. By enhancing antigen stability, prolonging immune stimulation, and enabling non-invasive administration routes such as oral and immersion vaccination, PLGA-based delivery systems represent a promising strategy for aquatic immunoprophylaxis. Their broader implementation may further reduce antibiotic reliance in aquaculture, thereby mitigating antimicrobial resistance and environmental impacts while supporting sustainable industry development.