Aqueous-Phase Synthesis of Hyaluronic Acid-Based Hydrogel Nanoparticles for Molecular Storage and Enzymatic Release

Polysaccharide-based hydrogel particles have attracted attention as promising carriers for various biomolecules and drugs owing to their biocompatibility and biodegradability. The network structure and hydrophilic features of these hydrogels result in large surface area and high water uptake, which allows them to effectively store active molecules. However, conventional protocols for synthesizing such hydrogel nanoparticles usually require high amounts of organic solvents and cross-linkers, which may cause potential toxicity issues. Herein, we present a method for the water-phase synthesis of hyaluronic acid-based hydrogel particles (HAGs) and their application for safely encapsulating biomolecules. By controlling the synthesis procedures and ingredients, the size and shape of the HAGs can be systematically optimized. The colloidal stability of the produced HAGs is evaluated by measuring their light-scattering properties under various conditions. The activity of loaded molecules, such as small antioxidants and large proteins, is also monitored via activity assays. Finally, controlled release of the loaded molecules is achieved via the enzymatic degradation of hyaluronic acid. We believe that the proposed HAGs could be used as promising carriers for protecting active ingredients from the outer environment to further develop biomedical and cosmetic products.