Humanin Nanoparticles for Reducing Pathological Factors Characteristic of Age-Related Macular Degeneration

Aum Solanki; Rudy Smalling; Abraham H Parola; Ilana Nathan; Roni Kasher; Yashwant Pathak; Vijaykumar Sutariya

doi:10.2174/1567201815666181031163111

Humanin Nanoparticles for Reducing Pathological Factors Characteristic of Age-Related Macular Degeneration

Curr Drug Deliv. 2019;16(3):226-232. doi: 10.2174/1567201815666181031163111.

Authors

Aum Solanki^{1

2}, Rudy Smalling¹, Abraham H Parola³, Ilana Nathan⁴, Roni Kasher⁵, Yashwant Pathak^{1

6}, Vijaykumar Sutariya¹

Affiliations

¹ Department of Pharmaceutical Sciences, USF College of Pharmacy, University of South Florida, Tampa, FL 33647, United States.
² USF Morsani College of Medicine, University of South Florida, Tampa, FL 33647, United States.
³ Department of Chemistry, The Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
⁴ Department of Clinical Biochemistry and Pharmacology, The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
⁵ Department of Desalination and Water Treatment, Zuckerberg Institute for Water Research, The Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede-Boquer Campus, Beersheba, 8499000, Israel.
⁶ Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia.

PMID: 30381074
DOI: 10.2174/1567201815666181031163111

Abstract

Background: Humanin is a novel neuronal peptide that has displayed potential in the treatment of Alzheimer's Disease through the suppression of inflammatory IL-6 cytokine receptors. Such receptors are found throughout the body, including the eye, suggesting its other potential applications. Age-related Macular Degeneration (AMD) is the leading cause of blindness in the developing world. There is no cure for this disease, and current treatments have several negative side effects associated with them, making finding other treatment options desirable.

Objective: In this study, the potential applications in treating AMD for a more potent humanin derivative, AGA-HNG, were studied.

Methods: AGA-HNG was synthesized and encapsulated in chitosan Nanoparticles (NPs), which were then characterized for their size, Encapsulation Efficiency (EE), and drug release. Their ability to suppress VEGF secretion and protect against oxidative apoptosis was studied in vitro using ARPE-19 cells. The chitosan NPs exhibited similar anti-VEGF properties and oxidative protection as the free protein while exhibiting superior pharmaceutical characteristics including biocompatibility and drug release.

Results: Drug-loaded NPs exhibited a radius of 346nm with desirable pharmacokinetic properties including a stable surface charge (19.5 ± 3.7 mV) and steady drug release capacity. AGA-HNG showed great promise in mediating apoptosis in hypoxic cells. They were also able to significantly reduce VEGF expression in vitro with reduced cellular toxicity compared to the free drug.

Conclusion: The ability of this drug delivery system to reduce retinal apoptosis with desirable pharmacokinetic and biocompatible properties makes this a promising therapeutic option for AMD.

Keywords: ARPE-19 cells; Nanoparticles; age-related macular degeneration; chitosan; humanin peptide; vascular endothelial growth factor..

MeSH terms

Cell Line
Cell Survival / drug effects
Chitosan / administration & dosage*
Chitosan / chemistry
Drug Delivery Systems
Drug Liberation
Humans
Intracellular Signaling Peptides and Proteins / administration & dosage*
Intracellular Signaling Peptides and Proteins / chemistry
Macular Degeneration
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Vascular Endothelial Growth Factor A / metabolism

Substances

Intracellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
humanin
Chitosan