Acetazolamide encapsulated dendritic nano-architectures for effective glaucoma management in rabbits

The present investigation was aimed to develop topically effective acetazolamide loaded poly(propylene imine) dendrimer nanoarchitectures and evaluate their intraocular pressure lowering potential. The 5.0G PPI dendrimers were synthesized using ethylendiamine as dendrimer core through divergent approach and characterized and loaded with acetazolamide (ACZ). The developed dendrimeric formulations were characterized for size, loading efficiency. The surface morphology of dendrimer was studied by Transmission Electron Microscopy. The developed dendrimer formulations were evaluated for hemolytic toxicity, ocular irritation index and intra ocular pressure reduction using normotensive adult male New Zealand albino rabbits as in vivo model. The maximum drug entrapment efficiency was found to be 56 +/- 2.3%. The in vitro release data of ACZ-5.0G PPI dendrimers showed sustained release of ACZ which was found to be 83.5 +/- 1.8 and 80.4 +/- 1.6% in phosphate buffer saline (pH 7.4) and simulated tear fluid (pH 7.4), respectively in 24 h. Ocular irritancy, ocular residence time and intraocular pressure lowering effect were performed. The study revealed that in lower concentrations the aqueous solutions of dendrimer formulations were found to be weakly irritant to the eyes. The sustained and prolonged reduction in intraocular pressure suggested that drug entrapped in dendrimers can be used for higher retention in ocular cul-de sac. Further, the PPI dendrimer based formulation seems to enhance the ocular drug residence time and exhibits better intraocular pressure lowering effect for glaucoma treatment, more safely, both in vitro and in vivo. (C) 2013 Elsevier B.V. All rights reserved.