Neuroprotective effect of melatonin loaded in ethylcellulose nanoparticles applied topically in a retinal degeneration model in rabbits

BESSONE CAROLINA; SOFIA MARTINEZ; JOSE D. LUNA; MARILYN A. MÁRQUEZ3; DANIEL ALLEMANDI; CARPENTIERI AGATA; DANIELA QUINTEROS

Cordoba

Encuentro; XXXIV Reunión Anual SAN 2019; 2019

SAN

During the development of different ocular pathologies, such as glaucoma, oxidative stress becomes the main cause of cellular damage. The antioxidant capacity of the cell is insufficient to protect the retinal ganglion cells (RGCs). Therefore, the exogenous administration of antioxidant agents is a promising strategy to inhibit some of the steps involved in the death of retinal cells. Melatonin (ME) has been described as being an effective antioxidant in the retina with direct and indirect free radical scavenging properties, and being able to protect the photoreceptor outer segment membranes from a free radical attack induced by light. Thisproject describes the elaboration of nanocapsules (NCECMEs) containing ME, and includes the formulation, physicochemical characterization, in vitro drug release, transcorneal permeation studies and an in vivo study of irritation. The neuroprotective effect of ME was also evaluated using the induced retinal degeneration (RD) model. In vitro ME release (1 and 2 mg/mL) from NCECMEs was found to be slower than ME solution. However, ex vivo assays demonstrated a higher permeation, attributable to the extended residence time of NCECMEs and also an ME effect on the membrane at low concentrations, leading to an increase in drug absorption. NCECMEs appeared to be more efficient for RGC protection, compared to ME solutions, against induced RD model, as indicated by damage indicators such as the apoptotic index (AI) and retina integrity.