Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model

Background/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a p...

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Main Authors: Sofia Mickaela Martinez, Ayelen Inda, Maximiliano Nicolás Ríos, Carolina del Valle Bessone, Abril Bruera Bossio, Mario Eduardo Guido, José Domingo Luna Pinto, Daniel Alberto Allemandi, Daniela Alejandra Quinteros
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Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/85
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author Sofia Mickaela Martinez
Ayelen Inda
Maximiliano Nicolás Ríos
Carolina del Valle Bessone
Abril Bruera Bossio
Mario Eduardo Guido
José Domingo Luna Pinto
Daniel Alberto Allemandi
Daniela Alejandra Quinteros
author_facet Sofia Mickaela Martinez
Ayelen Inda
Maximiliano Nicolás Ríos
Carolina del Valle Bessone
Abril Bruera Bossio
Mario Eduardo Guido
José Domingo Luna Pinto
Daniel Alberto Allemandi
Daniela Alejandra Quinteros
author_sort Sofia Mickaela Martinez
collection DOAJ
description Background/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. Methods: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Results: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Conclusions: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.
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spelling doaj-art-3e1b4086e26c49fc8186e93a24566bed2025-01-24T13:45:53ZengMDPI AGPharmaceutics1999-49232025-01-011718510.3390/pharmaceutics17010085Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal ModelSofia Mickaela Martinez0Ayelen Inda1Maximiliano Nicolás Ríos2Carolina del Valle Bessone3Abril Bruera Bossio4Mario Eduardo Guido5José Domingo Luna Pinto6Daniel Alberto Allemandi7Daniela Alejandra Quinteros8Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaCentro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaCentro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaÁrea de Cirugía Vítreo y Retina, Centro Privado de Ojos Romagosa S.A. y Fundación VER, Córdoba 5000, ArgentinaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, ArgentinaBackground/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. Methods: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Results: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Conclusions: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.https://www.mdpi.com/1999-4923/17/1/85human serum albumin nanoparticlesmelatoninneurodegenerative eye diseasesneuroprotection
spellingShingle Sofia Mickaela Martinez
Ayelen Inda
Maximiliano Nicolás Ríos
Carolina del Valle Bessone
Abril Bruera Bossio
Mario Eduardo Guido
José Domingo Luna Pinto
Daniel Alberto Allemandi
Daniela Alejandra Quinteros
Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
Pharmaceutics
human serum albumin nanoparticles
melatonin
neurodegenerative eye diseases
neuroprotection
title Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
title_full Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
title_fullStr Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
title_full_unstemmed Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
title_short Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model
title_sort neuroprotective effect of melatonin loaded in human serum albumin nanoparticles applied subconjunctivally in a retinal degeneration animal model
topic human serum albumin nanoparticles
melatonin
neurodegenerative eye diseases
neuroprotection
url https://www.mdpi.com/1999-4923/17/1/85
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