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

Abstract

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 1 week (160 h) 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.

Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation, Characterization, Cytotoxicity, Ex Vivo, and In Vivo Evaluation

“…Liposomes are small lipid vesicles composed of a phospholipid bilayer and are capable of delivering versatile drugs [12]. Different kinds of TM liposomes have been developed and proven to be able to enhance corneal permeability and extend effective time of drugs [13,14]. However, one major drawback of ocular liposomes is that they are prone to degradation, aggregation, and fusion [15,16].…”

Interaction of Coenzyme Q10 with Liposomes and its Impact on Suppression of Selenite – Induced Experimental Cataract

“…Pure DPPC vesicles upon dehydration when submitted to DSC analysis, showed a major endothermic peak at 105°C ( Figure 1 ), in accordance with previous studies. 12 , 13 The pre-transition temperature was around 80°C for empty DPPC liposomes. A sharp endothermic peak at about 75°C was observed for CoQ10 alone.…”

A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride

“…These structures have many favorable features, including good biocompatibility, non-immunogenicity and sustained release. 18,19 Furthermore, LPs have suitable particle size (PS) and ζ-potential (ZP), which can improve precorneal residence ability and drug uptake. 20 Therefore, LPs may be a good candidate for enhancing the ocular bioavailability of topically administered drugs.…”