Ocular Dorzolamide Nanoliposomes for Prolonged IOP Reduction: in-vitro and in-vivo Evaluation in Rabbits

Document Type: Research article

Authors

1 a Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran b Department of Pharmaceutics, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Ophthalmology, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular dorzolamide HCl nanoliposomes (DRZ – nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7:3 and 7:4 molar ratios of phosphatidylcholine:cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7:4 lipid ratio were evaluated in terms of drug release, physical stability and ex vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ – nanoliposomes or dorzolamide solution or marketed dorzolamid preparation (Biosopt®) and intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio entrapped greater amount of drug compared to those with 7:3 lipid components ratio. DRZ – nanoliposomes with 7:4 lipid ratio showed more transcorneal permeation than Dorzolamide solution (p<0.05); and the formulation prepared by TLH method exhibited higher permeability than that prepared by REV method (p<0.05). The selected DRZ – nanoliposomes showed greater IOP lowering activity and a more prolonged effect compared to dorzolamide solution and Biosopt®. DRZ – nanoliposomes prepared by TLH method with 7:4 ratio showed promising results as a candidate for the treatment of ocular hypertension.

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