PREPARATION AND EVALUATION OF ALGINATE/CHITOSAN NANODISPERSIONS FOR OCULAR DELIVERY

Abstract

Objective: Preparation and characterization of ketorolac tromethamine (KT)-loaded alginate/chitosan nanodispersions for ocular sustained drug delivery and improved transconeal permeation. Methods: Alginate/chitosan KT-loaded nanoparticles were formulated using different techniques; modified coaservation and ionotropic pregelation. The nanodispersions were evaluated for particle size, zeta potential, entrapment efficiency and in-vitro release. The formula with optimum physicochemical characteristics was tested for stability as well as ex-vivo transcorneal permeation in comparison to marketed eye drops (Acular®). Results: In both techniques, increasing the concentration of chitosan showed a significant increase in particle size. However, increased size with increasing the amount of alginate was significant in modified coaservation method but non-significant in ionotropic pregelation method. The ionotropic pregelation method generally resulted in nanoparticles with smaller sizes. The values of zeta potential were highly influenced by the alginate/chitosan ratio in both methods as the high amount of alginate shifted the zeta potential to be negative, and the absolute value increased by increasing its concentration. The entrapment of KT into nanoparticles prepared by ionotropic pregelation method was found to be significantly lower than those prepared by modified coaservation method. All the nanodispersions showed an initial burst release followed by a more gradual and sustained-release phase. Alginate NPs significantly retarded the release of KT and showed higher transcorneal permeation when compared with Acular®. Conclusion: Ionotropic pregelation method produced nanodispersions for all tested alginate/chitosan ratios with sustained KT release and improved transcorneal permeation.