Progress in Hyaluronan-Based Nanoencapsulation Systems for Smart Drug Release and Medical Applications

Hyaluronan (HA), a high-molecular-weight polysaccharide naturally found in vertebrate tissues such as skin, joints, and the vitreous body, plays a critical role in various biological processes. Its functionality is highly dependent on molecular weight, with high-molecular-weight HA exhibiting anti-inflammatory and immunosuppressive effects, while low-molecular-weight HA promotes inflammation, immunostimulation, and angiogenesis. Due to its biocompatibility, biodegradability, and tunable properties, HA has gained increasing attention in biomedical applications. This review summarizes recent advances in the encapsulation of HA with other polymers and therapeutic agents in nanosystems, particularly hydrogels and nanoparticles. HA-based formulations demonstrate improved therapeutic outcomes, including drug release sustained up to 7 days, wound closure rates exceeding 90% in animal models, particle size in the range of 50-300 nm, and enhanced bioavailability of encapsulated drugs by 2-3 fold compared with free drugs. Such properties have shown promise in enhancing therapeutic efficacy and targeted drug delivery in the treatment of skin wound healing, diabetes, osteoarthritis, rheumatoid arthritis, and ophthalmic diseases. The review emphasizes how HA's modifications and composite systems optimize drug release profiles and biological interactions, thereby contributing to the development of next-generation biomedical therapies.