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. (C) 2011 Elsevier Ltd. All rights reserved.