Enhancement of ocular anti-glaucomic activity of agomelatine through fabrication of hyaluronic acid modified-elastosomes: formulation, statistical optimisation, in vitro characterisation, histopathological study, and in vivo assessment.

Abstract

Aim: The aim of this manuscript was to fabricate agomelatine (AGM) loaded elastosomes to improve its corneal permeation and ocular bioavailability. AGM is a biopharmaceutical classification system (BCS) class II with low water solubility and high membrane permeability. It has a potent agonistic action on melatonin receptors, so it is used for glaucoma treatment.

Methods: Elastosomes were made using modified ethanol injection technique according to a 2² × 4¹ full factorial design. The chosen factors were: edge activators (EAs) type, surfactant percent (SAA %w/w), and cholesterol:surfactant ratio (CH:SAA ratio). The studied responses were encapsulation efficiency percent (EE%), mean diameter, polydispersity index (PDI), zeta potential (ZP), percentage of drug released after two hours (Q_2h%), and 24 hours (Q_24h%).

Results: The optimum formula with the desirability of 0.752 was composed of Brij98 as EA type, 15%w/w SAA%, and 1:1 CH:SAA ratio. It revealed EE% of 73.22%w/v and mean diameter, PDI, ZP, Q_2h%, and Q_24h% values of 484.25 nm, 0.31, -30.75 mV, 32.7%w/v, and 75.6%w/v, respectively. It demonstrated acceptable stability for three months and superior elasticity than its conventional liposome. The histopathological study ensured the tolerability of its ophthalmic application. Also, it was proven to be safe from the results of the pH and refractive index tests. The in vivo pharmacodynamic parameters of the optimum formula revealed dominance in a maximum % decrease in intraocular pressure (IOP), the area under the IOP response curve, and mean residence time with the value of 82.73%w/v, 820.69%h, and 13.98 h compared to that of the AGM solution (35.92%w/v, 181.30%h, and 7.52 h).

Conclusions: Elastosomes can be a promising option to improve AGM ocular bioavailability.