Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium

The ocular immune privilege is a phenomenon brought about by anatomical and physiological barriers to shield the eye from immune and inflammation responses. While this phenomenon is beneficial for eyes protection, it is, at the same time, a hindrance for drug delivery to the posterior segment of the...

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Main Authors: Amine Laradji, Bedia B. Karakocak, Alexander V. Kolesnikov, Vladimir J. Kefalov, Nathan Ravi
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/13/19/3324
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author Amine Laradji
Bedia B. Karakocak
Alexander V. Kolesnikov
Vladimir J. Kefalov
Nathan Ravi
author_facet Amine Laradji
Bedia B. Karakocak
Alexander V. Kolesnikov
Vladimir J. Kefalov
Nathan Ravi
author_sort Amine Laradji
collection DOAJ
description The ocular immune privilege is a phenomenon brought about by anatomical and physiological barriers to shield the eye from immune and inflammation responses. While this phenomenon is beneficial for eyes protection, it is, at the same time, a hindrance for drug delivery to the posterior segment of the eye to treat retinal diseases. Some ocular barriers can be bypassed by intravitreal injections, but these are associated with several side effects and patient noncompliance, especially when frequent injections are required. As an alternative, applying drugs as an eye drop is preferred due to the safety and ease. This study investigated the possible use of topically-applied hyaluronic acid-coated gold nanoparticles as drug delivery vehicles to the back of the eye. The coated gold nanoparticles were topically applied to mouse eyes, and results were compared to topically applied uncoated gold nanoparticles and phosphate-buffered saline (PBS) solution. Retina sections from these mice were then analyzed using fluorescence microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). All characterization techniques used in this study suggest that hyaluronic acid-coated gold nanoparticles have higher distribution in the posterior segment of the eye than uncoated gold nanoparticles. Electroretinogram (ERG) analysis revealed that the visual function of mice receiving the coated gold nanoparticles was not affected, and these nanoparticles can, therefore, be applied safely. Together, our results suggest that hyaluronic acid-coated gold nanoparticles constitute potential drug delivery vehicles to the retina when applied noninvasively as an eye drop.
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spelling doaj.art-859a4728a5c84c15ae2fd92000e4d9c62023-11-22T16:38:58ZengMDPI AGPolymers2073-43602021-09-011319332410.3390/polym13193324Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment EpitheliumAmine Laradji0Bedia B. Karakocak1Alexander V. Kolesnikov2Vladimir J. Kefalov3Nathan Ravi4Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USADepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USADepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USAThe ocular immune privilege is a phenomenon brought about by anatomical and physiological barriers to shield the eye from immune and inflammation responses. While this phenomenon is beneficial for eyes protection, it is, at the same time, a hindrance for drug delivery to the posterior segment of the eye to treat retinal diseases. Some ocular barriers can be bypassed by intravitreal injections, but these are associated with several side effects and patient noncompliance, especially when frequent injections are required. As an alternative, applying drugs as an eye drop is preferred due to the safety and ease. This study investigated the possible use of topically-applied hyaluronic acid-coated gold nanoparticles as drug delivery vehicles to the back of the eye. The coated gold nanoparticles were topically applied to mouse eyes, and results were compared to topically applied uncoated gold nanoparticles and phosphate-buffered saline (PBS) solution. Retina sections from these mice were then analyzed using fluorescence microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). All characterization techniques used in this study suggest that hyaluronic acid-coated gold nanoparticles have higher distribution in the posterior segment of the eye than uncoated gold nanoparticles. Electroretinogram (ERG) analysis revealed that the visual function of mice receiving the coated gold nanoparticles was not affected, and these nanoparticles can, therefore, be applied safely. Together, our results suggest that hyaluronic acid-coated gold nanoparticles constitute potential drug delivery vehicles to the retina when applied noninvasively as an eye drop.https://www.mdpi.com/2073-4360/13/19/3324gold nanoparticleshyaluronic acidsurface functionalizationtransmission electron microscopyinductively coupled plasma mass spectrometrybiocompatibility
spellingShingle Amine Laradji
Bedia B. Karakocak
Alexander V. Kolesnikov
Vladimir J. Kefalov
Nathan Ravi
Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
Polymers
gold nanoparticles
hyaluronic acid
surface functionalization
transmission electron microscopy
inductively coupled plasma mass spectrometry
biocompatibility
title Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
title_full Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
title_fullStr Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
title_full_unstemmed Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
title_short Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium
title_sort hyaluronic acid based gold nanoparticles for the topical delivery of therapeutics to the retina and the retinal pigment epithelium
topic gold nanoparticles
hyaluronic acid
surface functionalization
transmission electron microscopy
inductively coupled plasma mass spectrometry
biocompatibility
url https://www.mdpi.com/2073-4360/13/19/3324
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