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

MARTINEZ, SOFIA M.; INDA, AYELÉN; RIOS, MAXIMILIANO N.; ALLEMANDI, DANIEL A.; GUIDO, MARIO; QUINTEROS, DANIELA A.

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas. RICiFa.; 2023

RICiFa

In the field of nanotechnology applied to therapeutics, nanoparticles have emerged as effectivecarriers 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 relevantoption, given their inherent characteristics of biodegradability, biocompatibility, and absence ofantigenic activity. This protein, widely present in the body, represents a promising vehicle fortransporting insoluble drugs, including melatonin (Mel), which possesses beneficial anti-apoptoticand antioxidant properties for the treatment of neurodegenerative ocular diseases.The purpose of this research is to evaluate the neuroprotective effect of these nanoparticles (NpHSA-Mel) in ocular neurodegenerative diseases, highlighting their stability, low toxicity and capacityfor 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 Lbuthionine-S,R-sulfoximine, triggered apoptosis in retinal ganglion cells. To evaluate the efficacy ofsubconjunctivally administered Np-HSA-Mel, flow cytometry assays on isolated rabbit retina,histological sections, TUNEL technique and pupillometry studies were performed. These assaysallowed correlating cell survival and apoptotic index ex-vivo with in-vivo pupillary function, minimisingthe 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 reduceapoptosis in retinal cells, exerting a neuroprotective effect on total cells and specifically on the retinalganglion cell layer, with statistically significant differences in both cases. Finally, in-vivo pupillometryassays showed no significant alterations in pupillary contraction response in Np-HSA-Mel-treatedeyes relative to untreated MDR-affected eyes. These results suggest a promising therapeuticpotential for Np-HSA-Mel in the treatment of ocular neurodegenerative diseases.