Preparation and characterization of hyaluronic acid-based hydrogel nanoparticles

Abstract

Novel polymeric amphiphilic hydrogel nanoparticles have been prepared by covalent attachment of hydrophobic tetradecylamine (TDA) to hyaluronic acid (HA) in the presence of 1-ethyl-3(3-dimethylaminopropyl)carbodiimide and N-hydroxysulfosuccinimide. Their chemical structure and self-association behavior in an aqueous solution were investigated by using H-1 NMR, dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy (TEM). Owing to their amphiphilic characteristics, the resulting conjugates could form self-assembled hydrogel nanoparticles in an aqueous phase via the intra- or intermolecular association of hydrophobic moieties conjugated to the backbone of HA. From the TEM results, it was observed that the hydrogel nanoparticles were spherical in shape. The particle sizes and critical aggregation concentrations (CACs) of the conjugates were significantly dependent on the degree of substitution (DS) of TDA. The CACs of the conjugates were as low as 50-180 mu g/mL; this suggests that the conjugates can form nanoparticles in diluted aqueous media such as body fluids. The mean diameters of the nanoparticles decreased as the DS of TDA increased, indicating that a larger amount of hydrophobic moieties in the conjugate allows formation of compact hydrophobic inner cores. It is anticipated that this HA-based nanoparticles can be used as new drug carriers for biomedical applications. (c) 2007 Elsevier Ltd. All rights reserved.