Nanoparticle-reinforced polysaccharide hydrogels in drug delivery systems: A review of recent progress

Polysaccharide nanoparticle-reinforced hydrogels are an emerging class of adaptive drug delivery platforms that go beyond the limitations of conventional hydrogel matrices. Upon integrating nanoscale polysaccharide building blocks into three-dimensional hydrogel networks, these composite systems achieve synergistic improvements in mechanical robustness, drug encapsulation efficiency, and controlled release behavior. Importantly, the intrinsic bioactivity of polysaccharides, such as the overcoming of drug resistance targeting by hyaluronic acid, mucoadhesion, and permeation enhancement by chitosan or pH-responsive gelation of alginate, enables selective interactions with diseased tissues, thus offering opportunities for microenvironment-guided therapeutic delivery. Recent advances evidence their applicability in oncology, wound regeneration, antimicrobial therapy, and injectable minimally invasive therapeutics, where stimuli-responsive degradation and receptor-mediated uptake significantly enhance the precision of treatment and reduce systemic toxicity. Despite these promising features, batch variability, nanoparticle dispersion stability, and the absence of standardized evaluation metrics remain critical barriers to clinical translation. The present review consolidates recent progress in the formulation strategies, structure-function relationships, and biomedical applications of polysaccharide nanoparticle-loaded hydrogels, while emphasizing regulatory, manufacturing, and scalability considerations. Finally, key future directions are outlined, emphasizing the need for cross-platform characterization standards, in vivo biodegradation mapping, and integration into personalized therapeutic regimens to accelerate their transition toward clinically deployable drug delivery systems.