The extended ocular hypotensive effect of positive liposomal cholesterol bound timolol maleate in glaucomatous rabbits.

Increased intraocular pressure (IOP) is a significant risk factor for the development of glaucoma. Timolol maleate is a beta-adrenergic receptor blocking agent and it is used for the treatment of glaucoma in order to reduce the elevated IOP that is characteristic of this eye disease. Systemic toxicity from topical timolol occurs more frequently than local toxicity and can affect the pulmonary, cardiac and central nervous systems. The objective of the present study, therefore, was to formulate multilamellar vesicles (MLVs) liposomal preparations of timolol maleate using their advantage of being less toxic compared with non-liposome-based drugs to be applied topically and to evaluate the in vivo performance of the prepared liposomes to extend the time of reduced IOP of glaucomatous rabbit's eye measured using a standard Shiotz tonometer. The encapsulation efficiency of MLVs was measured using a spectrophotometric technique. Differential scanning calorimetry (DSC) was used to monitor the effects of timolol maleate in the absence and presence of cholesterol on liposome thermal behaviour. Positively charged MLVs of timolol in the presence of a lower amount of cholesterol (DPPC(7):Chol(2):Timolol(2):SA(1) molar ratio) were found to be superior compared with other formulations in extending the ocular hypotensive effect approximately for 1week (160h) which encourages its physiological effectiveness. The increase of the cholesterol molar ratio in the prepared liposomal formulations serves to decrease the permeability of the lipid bilayer that is manifested by a low rate of drug release, an increased percentage of entrapment efficiency and a consequently lower bioavailability. Copyright (C) 2011 John Wiley & Sons, Ltd.