Chitosan/sulfobutylether-β-cyclodextrin nanoparticles as a potential approach for ocular drug delivery

Development of efficient ocular delivery nanosystems remains a major challenge to achieve sustained therapeutic effect. The purpose of this work was to develop chitosan nanoparticles using sulfobutylether-beta-cyclodextrin (SBE-beta-CD) as polyanionic crosslinker and to investigate the potential of using those nanostructures as ocular drug delivery systems. Econazole nitrate (ECO) was chosen as model drug molecule. The influence of different process variables (chitosan molecular weight and the concentration of the two ionic agents) on particle size, polydispersity index, zeta potential, drug content, in vitro release and mucoadhesive properties was investigated. The results showed that the prepared nanoparticles were predominant spherical in shape having average particle diameter from 90 to 673 nm with positive zeta potential values from 22 to 33 mV and drug content values ranging from 13 to 45%. Drug release from optimized nanoparticles was controlled with approximately 50% of the original amount released over a 8 h period. The release profile of nanoparticles followed a zero-order release kinetics. The optimized nanoparticles were tested for their use as ocular drug delivery systems on albino rabbits. The in vivo studies revealed that the prepared mucoadhesive nanoparticles had better ability in sustaining the antifungal effect of ECO than the ECO solution. Therefore, chitosan/SBE-beta-CD nanoparticles developed showed a promising carrier for controlled delivery of drug to the eye. (C) 2011 Elsevier B.V. All rights reserved.