Novel crosslinked nanoparticles of chitosan oligosaccharide and dextran sulfate for ocular administration of dorzolamide against glaucoma

Abstract

Glaucoma is related to the damaged optic nerve leading to the development of high intraocular pressure. Currently, 12 million people in India suffer from glaucoma, making it the third leading cause of blindness. Elevated intraocular pressure is one of the significant risk factors aggravating glaucoma. Dorzolamide hydrochloride (DRZ) is available as eye drop to address these issues. The eye drop has a short residence time, limited permeability, and some degree of ionization leading to poor bioavailability in the ocular cavity. Therefore, the chitosan oligosaccharide (CSO)-dextran sulfate (DS) crosslinked nanoparticles (DRZ–CSO–DS-NPs) were formulated with specified objectives of improving the mucoadhesion, penetration, and ocular delivery of dorzolamide (DRZ) to elicit antiglaucoma activity. The NPs were synthesized using an ionic gelation process with the application of the Box-Behnken experimental design. The concentrations of CSO and DS suitable for the delivery of DRZ have been statistically optimized. The results revealed that the optimum formula showed particle size of 142.8 ± 2.1 nm, polydispersity index (PDI) 0.139 ± 1.2, zeta potential of +24.2 ± 5.3 mV, entrapment efficiency of 92.12 ± 0.8%, and prolonged release for 12 h. The in vivo ocular hypotensive experiment suggests a significant reduction in intraocular pressure (41.56%) that declined for another 10 h. The Hen's egg test-chorioallantoic membrane (HET-CAM) study further disclosed that the DRZ–CSO–DS-NPs were non-irritating, hemocompatible, and suitable for ocular administration. The promising results obtained after in vivo and in vitro evaluation of topically administered DRZ–CSO–DS-NPs demonstrated it as an alternative strategy for developing mucoadhesive nanocarriers with enhanced therapeutic efficacy for ocular delivery of DRZ.