June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
NEUROPROTECTIVE EFFECT OF MELATONIN LOADED IN ETHYLCELLULOSE NANOPARTICLES APPLIED TOPICALLY IN A RETINAL DEGENERATION MODEL IN RABBITS
Author Affiliations & Notes
  • Jose D Luna Pinto
    Ophthalmology, Ctr Privado de Ojos Romagosa-Fndtn VER, Mendiolaza, Argentina
  • Carolina del Valle Bessone
    pharmacology, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Cordoba, Cordoba, Argentina
  • Sofía Mickaela Martinez
    pharmacology, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Cordoba, Cordoba, Argentina
  • Marilyn Ann Marquez
    ophthalmology, Duke University eye center, Durham, North Carolina, United States
  • Daniel Allemandi
    pharmacology, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Cordoba, Cordoba, Argentina
  • Ágata Carpentieri
    Instituto de Investigación en Ciencias de la Salud (INICSA), CONICET- Universidad Nacional de Córdoba and Cátedra B de Química Biológica, Facultad de Odontología, Universidad Nacional de Córdoba, Argentina
  • Daniela Quinteros
    pharmacology, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Cordoba, Cordoba, Argentina
  • Footnotes
    Commercial Relationships   Jose Luna Pinto, None; Carolina del Valle Bessone, None; Sofía Martinez, None; Marilyn Marquez, None; Daniel Allemandi, None; Ágata Carpentieri, None; Daniela Quinteros, None
  • Footnotes
    Support  ConsejoNacional de InvestigacionesCientíficas y Técnicas (CONICET), FONCyT PICTPréstamo BID PICT Nº 4316/2013 and SECyT-UNC Nº366_
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2897. doi:
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      Jose D Luna Pinto, Carolina del Valle Bessone, Sofía Mickaela Martinez, Marilyn Ann Marquez, Daniel Allemandi, Ágata Carpentieri, Daniela Quinteros; NEUROPROTECTIVE EFFECT OF MELATONIN LOADED IN ETHYLCELLULOSE NANOPARTICLES APPLIED TOPICALLY IN A RETINAL DEGENERATION MODEL IN RABBITS. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2897.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Different ocular pathologies, such as glaucoma and other retinopathies, oxidative stress becomes a significant cause of cellular damage. Intravitreal injection of exogenous melatonin (ME) protects retinal ganglion cells from degeneration and apoptosis in experimental models of the retina. The objective of the present work was to prepare and characterize NC loaded with ME using ethyl cellulose (EC) as encapsulating polymer.

Methods : These formulations were evaluated after the topical ophthalmic application in rabbits with previously induced retinal degeneration (RD) model. We prepared NCECMEs 1 and 2 mg/ml by interfacial deposition of preformed polymers. We characterized the formulations in terms of particle size, electrokinetic potential, pH, osmolarity, loading capacity, and encapsulation efficiency. The particle structures of the NCECMEs were observed and analyzed by Field Emission Scanning Electron Microscopy (FE-SEM Σigma, Carl Zeiss). In vitro drug release and transcorneal permeation assay were performed in a modified Franz diffusion assembly at 35.0 ± 0.5°C coupled with UV spectroscopy technique. We evaluated the neuroprotective effect of ME using a retinal degeneration (RD) model in rabbits using a single dose of glutamate (GLUT) and L-Butionine-S, R-Sulfoximine (BSO).

Results : Particle size of the NPs thus obtained (NCECME) ranged from 150 nm to 170 nm. Polydispersity Index (PDI) was less than 0.120 and the measured electrokinetic potential was approximately -15 mV, with the encapsulation efficiency being approximately 60%. The pH of the aqueous dispersion was around 4-5 and the osmolality properties of the NCECME dispersions were very close to those of tears. 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 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.

Conclusions : These findings add new perspectives to the current knowledge concerning the topical administration of neuroprotectors as melatonin for the treatment of retinal degeneration diseases.

This is a 2020 ARVO Annual Meeting abstract.

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