Hyaluronic acid hydrogel particles with tunable charges as potential drug delivery devices

We report the synthesis of hyaluronic acid (HA) particles with positive and negative charges on their surfaces. HA-based particles were prepared using an aqueous solution of linear HA in a sodium bis(2-ethylhexyl) sulfosuccinate (AOT)–isooctane microemulsion system. The prepared HA particles were post modified, i.e., oxidized to aldehyde (HA-O) by NaIO4 treatment and then these HA-O particles were reacted with cysteamine (CYs) to obtain thiol groups on the surface of the HA particles. The thiolated HA particles (HA-CYs) were further exposed to radical polymerization with an anionic monomer, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), and with a cationic monomer, 3-acrylamidopropyl-trimethylammonium chloride (APTMACl), to generate HA-based ionic hydrogel particles, HA-CYs-AMPS and HA-CYs-APTMACl, respectively. The prepared HA-based anionic and cationic particles illustrated strong pH dependent size variations. We demonstrated that HA-CYs-AMPS and HA-CYs-APTMACl particles can be used as drug delivery vehicles. Trimethoprim (TMP) and naproxen (NN) were used as model drugs in the drug delivery experiments.