Topical delivery of macitentan self-nanoemulsion for ocular anti-inflammation potential and effect of cosurfactant

Abstract

Macitentan is an approved orally active endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension (PAH). It is poorly soluble and also exerts slow absorption after oral administration. Endothelins play a major role in vascular hemostasis and ocular inflammatory reactions. Self-nanoemulsifying drug delivery systems (SNEDDS) of macitentan were prepared using an oil-surfactant mix, and PEG 600, Transcutol HP, or ethanol as co-surfactant. The potentiality of ocular anti-inflammation has also been examined after the administration of macitentan delivery systems of self-nanoemulsion in a carrageenan-induced (upper palpebral region: 100 μl, 3 % w/v) rabbit eye model. Nanoemulsion regions were identified of macitentan-loaded SNEDDS formulation after constructing ternary diagrams. Formulation containing Transcutol HP (MT2) exhibited globule size (47.35 ± 0.295 nm), PDI (0.191 ± 0.008), and zeta potential (-12.0 ± 0.81) with highest corneal permeation of about 90 % in 6 h compared to PEG 600 as cosurfactant. Improved corneal permeation has been observed after topical application of self-nanoemulsion containing Transcutol HP. Symptoms of ocular inflammation disappeared within 1 h after MT2 instillation in carrageenan-induced rabbit eye whereas, more than 2 h of acute inflammation continued in the untreated eye. Macitentan self-nanoemulsion containing Transcutol HP could be used for the management of ocular inflammation.