Preparation of hyaluronan nanoparticles using different cross-linking strategies

Abstract

Nowadays, the use of drug-delivery systems becomes more and more popular. The use of the supporting medium for drug substances may serve to delay and control the drug release. Biodegradable polymers, such as hyaluronic acid (HA), represent the most natural materials beneficially used for such systems. In this work, we focused on the preparation of hyaluronic acid nanoparticles using low-molecular weight HA (LMW-HA; 11 and 30 kDa) which is rarely used because the size of the obtained particles is usually higher than those of the high-molecular weight form. To verify the suitability of LMW-HA for the preparation of nano-scale particles, different cross-linking strategies were chosen. The hydrodynamic diameters of prepared nanoparticles and the structure compactness were then compared. Adipic acid dihydrazide was used as a conventional cross-linker which leads to monodisperse nanoparticles (186 nm, 255 nm resp.) and compact structure. The use of bis(3-aminopropyl)amine as a novel approach for covalent cross-linking of HA results in the particles with higher hydrodynamic diameters (592 nm, 317 nm resp.) and with less compact structure. Both strategies were then combined with a goal to reduce the hydrodynamic diameters to the nanoscale format and tighter structure. The results obtained has shown a slight improvement (208 nm, 286 nm resp.), but with negligible effect on the structure of particles.