Ocular hypotensive efficacy of a new liposomal latanoprost formulation administered by different routes for experimental ocular hypertension

Abstract

Background: Prostaglandin analogs (e.g., latanoprost) are the first-line therapy for glaucoma. These medications, however, have a short antihypertensive effect due to low penetration of topical drug across the corneal epithelium, which causes the need for their daily application for a long time. Therefore, it is clinically and socially important to develop latanoprost medications with improved efficacy against ocular hypertension (OHT) and with improved patient compliance through the prolonged effect of latanoprost. Purpose: To assess (a) changes in intraocular pressure (IOP) with time and (b) duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT. Material and Methods: Twenty-one adult Chinchilla rabbits (age, 1 year; weight, 2.5 to 3.0 kg) were divided into three groups: group 1, animals with induced OHT, which was treated with topical liposomal latanoprost (n = 7); group 2, animals with induced OHT, which was treated with a single subconjunctival injection of liposomal latanoprost (n = 7); and group 3, untreated animals with induced OHT, (n = 7). OHT was induced by two 0.1-mL anterior chamber injections of 0.3% carbomer at 10 day intervals. A 0.1-ml subconjunctival injection of liposomal latanoprost formulation was applied immediately after formation of the model of OHT. Topical liposomal latanoprost (one drop per eye) was bilaterally applied at a dose of 1 drop per eye once daily in the evening. Follow-up duration was 10 weeks. IOP was measured in each group before and after OHT modeling. In addition, it was measured after subconjunctival injection of liposomal latanoprost or first application of topical liposomal latanoprost. Thereafter, IOP measurements were performed once a week. Statistica 5.5 (StatSoft, Tulsa, OK, USA) software was applied for statistical analysis. Non-parametric statistical tests for dependent and independent samples were used. Results: We assessed the pharmacological efficacy and duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT in rabbits. After OHT modeling was performed, there was a persistent increase in IOP, with the IOP values being 51-65% higher than at baseline (р < 0.001). The IOP in animals with OHT treated daily with topical liposomal latanoprost was 30.5% lower than in untreated animals with OHT (р < 0.001). A single subconjunctival injection of the examined liposomal latanoprost formulation resulted in a 36.7% reduction in IOP compared to baseline (р ˂ 0.001), with the effect being as long as 10 weeks. Conclusion: The current study demonstrated a statistically significant hypotensive effect of topical or subconjunctival injection treatment with the examined liposomal latanoprost formulation, with the effect of a single subconjunctival injection of the formulation being as long as 10 weeks.

Keywords

• liposomal latanoprost formulation
• experimental ocular hypertension
• intraocular pressure