Betaxolol Hydrochloride Loaded Chitosan Nanoparticles for Ocular Delivery and their Anti-glaucoma Efficacy

Kunal      Jain; R.   Suresh   Kumar; Sumeet      Sood; G.      Dhyanandhan

Abstract

Many effective anti-glaucoma drugs available for the treatment of ocular hypertension and open angle glaucoma are associated with rapid and extensive precorneal loss caused by the drainage and high tear fluid turnover. The present study involved design of mucoadhesive nanoparticulate carrier system containing betaxolol hydrochloride for ocular delivery to improve its corneal permeability and precorneal residence time. Nanoparticles were prepared by spontaneous emulsification method and had a particle size of 168-260nm with zeta potential of 25.2-26.4 mV. The in vitro release studies in simulated tear fluid exhibited biphasic release pattern with an initial burst followed by sustained release upto 12 h. The sterility tests confirmed that formulation was free from viable microorganisms and suitable for ocular delivery. The ocular tolerance of nanoparticles was evaluated using Hen Egg-Chorion Allantoic Membrane (HE-CAM) method and was found to be non-irritant. Stability studies of nanoparticles revealed that there was no significant change in particle size and drug content after storage at 25±2°C/60±5% RH over a period of 3 months. In vivo pharmacodynamic studies were carried out in dexamethasone induced glaucoma model in rabbits. The developed nanoparticles showed significant decrease in intraocular pressure (IOP) compared to marketed formulation. Optimized formulation of BN3 showed gradual reduction of IOP reaching peak value of 9.9±0.5mm Hg, equivalent to 36.39±1.84% reduction in IOP compared to control at the end of 5 h which was significant (p < 0.05) compared to marketed formulation. Thus, our studies demonstrate that developed nanoparticles offer a promising delivery system for the management of glaucoma.

Keywords: Betaxolol, glaucoma, chitosan, nanoparticles, ocular delivery.