Human Serum Albumin Nanoparticles Loaded with Melatonin, a promising Therapeutic Strategy for the Treatment of Neurodegenerative Ocular Diseases

MATINEZ SOFIA; INDA AYELEN; RIOS MAXIMILIANO; MARIO GUIDO; ALBERTO ALLEMANDI, DANIEL; DANIELA QUINTEROS

Rosario

Encuentro; 7ma Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2023); 2023

UNR

In the field of nanotechnology applied to therapeutics, nanoparticles have emerged as effective carriers for controlled drug delivery due to their ability to interact specifically with cells and tissues. In this context, nanoparticles based on Human Serum Albumin (HAS) have emerged as a relevant option, given their inherent characteristics of biodegradability, biocompatibility, and absence of antigenic activity. This protein, widely present in the body, represents a promising vehicle for transporting insoluble drugs, including melatonin (Mel), which possesses beneficial anti-apoptotic and antioxidant properties for the treatment of neurodegenerative ocular diseases.The purpose of this research is to evaluate the neuroprotective effect of these nanoparticles (Np-HSA-Mel) in ocular neurodegenerative diseases, highlighting their stability, low toxicity and capacity for controlled release of melatonin, previously evaluated.In order to evaluate the neuroprotective effect of the system, a model of retinal degeneration (MDR) was used in albino rabbits. This model, induced by oxidative agents such as glutamate and L-buthionine-S,R-sulfoximine, triggered apoptosis in retinal ganglion cells. To evaluate the efficacy of subconjunctivally administered Np-HSA-Mel, flow cytometry assays on isolated rabbit retina, histological sections, TUNEL technique and pupillometry studies were performed. These assays allowed correlating cell survival and apoptotic index ex-vivo with in-vivo pupillary function, minimising the use of animals and contributing to the compliance with the 3Rs in experimental animals.The results obtained indicate the potential of Np-ASH-Mel nanoparticles to significantly reduce apoptosis in retinal cells, exerting a neuroprotective effect on total cells and specifically on the retinal ganglion cell layer, with statistically significant differences in both cases. Finally, in-vivo pupillometry assays showed no significant alterations in pupillary contraction response in Np-HSA-Mel-treated eyes relative to untreated MDR-affected eyes. These results suggest a promising therapeutic potential for Np-HSA-Mel in the treatment of ocular neurodegenerative diseases