Abstract
Dual-drug delivery systems using hydrogel-nanoparticle composites have emerged as a versatile platform for achieving controlled, targeted, and efficient delivery of two distinct therapeutic agents. This approach combines the high loading capacity and tunable release properties of hydrogels with the enhanced stability and targeting ability of nanoparticles, providing synergistic benefits in various biomedical applications. While significant progress has been made, previous research has primarily focused on single-drug systems or simple co-delivery strategies, often lacking precise spatial and temporal control. This gap underscores the need for more sophisticated composite designs that enable programmable, multi-phase release. This review discusses representative fabrication methods, including physical embedding, covalent integration, and layer-by-layer assembly, to offer insights into practical implementation strategies. Also we present recent studies focusing on key applications-including wound healing, cancer therapy, infection prevention, transplant immunosuppression, and tissue regeneration-with an emphasis on composite design and formulation strategies, types of hydrogels and nanoparticles, and mechanisms of dual-drug release and evaluation. Recent advances in nanoparticle engineering and hydrogel formulation have enabled precise control over drug release and improved therapeutic outcomes. Dual-drug delivery systems using hydrogel-nanoparticle composites present a promising approach for overcoming the limitations of conventional monotherapy and achieving synergistic therapeutic effects. Ongoing research continues to optimize the design, efficacy, and safety of these systems, paving the way for their clinical translation.