Advances in Bioactive Polysaccharide—Small-Molecule Drug Supramolecular Nanocomplexes for Drug Delivery and Therapeutic Applications

Bioactive polysaccharides such as fucoidan, β-glucans, and medicinal plant polysaccharides contain functional groups that can interact with drug molecules, and some of them also retain their own biological activities. Through reversible noncovalent interactions, these polysaccharides can associate with small-molecule drugs and form supramolecular nanocomplexes. This review discusses hydrogen bonding, hydrophobic association, electrostatic complexation, π–π stacking, and the cooperation among these interactions. The effects of pH, ionic strength, concentration, and solvent composition on assembly behavior are also considered. Nanoprecipitation/solvent exchange, polyelectrolyte complexation, direct aqueous self-assembly, and microfluidic-assisted assembly are compared in terms of nanostructure formation, process control, and reproducibility. Evidence from molecular, colloidal, solid-state, and computational characterization is considered together to clarify the relationship between structure, assembly, and performance. Reported benefits include improved drug dispersibility, colloidal stability, release control, bioavailability, cellular uptake, biodistribution, and safety. In some systems, the polysaccharide component may also contribute to therapeutic effects in tumors, inflammatory diseases, infected wounds, and local regenerative matrices. Quantitative mechanism studies, polysaccharide standardization, biocompatibility assessment, process scale-up, and long-term safety evaluation remain necessary for the further development of these drug delivery systems.