Hydrogel-based strategies for the controlled delivery of analgesic and anti-inflammatory drugs

Abstract In clinical practice, drug encapsulation is an important strategy for enhancing therapeutic efficacy and reducing adverse effects. This review critically examines how polymer origin, crosslinking strategy, swelling behavior, degradation rate, and three-dimensional network architecture influence drug loading, protection, release kinetics, and therapeutic performance in hydrogel-based drug delivery systems. Based on a comparative analysis of hydrogel formulations, relationships among polymer composition, crosslinking mechanisms, drug-loading capacity, and release behavior are identified, highlighting current design trends and remaining gaps in stimuli-responsive systems. Hydrogels are presented as versatile encapsulation matrices that retain drugs through ionic interactions, chemical conjugation, and physical entrapment, while also enabling stimuli-responsive release. Controlled drug release mechanisms, including diffusion, swelling, erosion, and responses to pH, temperature, enzymes, and inflammatory microenvironments, are also discussed. Overall, the available evidence indicates that hydrogels can serve as effective drug encapsulation matrices by improving the stability of active compounds, bioavailability, local retention, and targeted drug release while reducing systemic toxicity. These findings reinforce the potential of hydrogel-based drug delivery systems for the development of safer, more effective, and personalized analgesic and anti-inflammatory therapies.