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Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye

Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. The...

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Autores principales: Tsai, Cheng-Han, Hoang, Le Ngoc, Lin, Chun Che, Pan, Liang-Chen, Wu, Chiao-Li, Lin, I-Chan, Wang, Peng-Yuan, Tseng, Ching-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228085/
https://www.ncbi.nlm.nih.gov/pubmed/35745825
http://dx.doi.org/10.3390/pharmaceutics14061253
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author Tsai, Cheng-Han
Hoang, Le Ngoc
Lin, Chun Che
Pan, Liang-Chen
Wu, Chiao-Li
Lin, I-Chan
Wang, Peng-Yuan
Tseng, Ching-Li
author_facet Tsai, Cheng-Han
Hoang, Le Ngoc
Lin, Chun Che
Pan, Liang-Chen
Wu, Chiao-Li
Lin, I-Chan
Wang, Peng-Yuan
Tseng, Ching-Li
author_sort Tsai, Cheng-Han
collection PubMed
description Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH−) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH− NPs were 390.0 nm and −35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2–50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier.
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spelling pubmed-92280852022-06-25 Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye Tsai, Cheng-Han Hoang, Le Ngoc Lin, Chun Che Pan, Liang-Chen Wu, Chiao-Li Lin, I-Chan Wang, Peng-Yuan Tseng, Ching-Li Pharmaceutics Article Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH−) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH− NPs were 390.0 nm and −35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2–50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier. MDPI 2022-06-13 /pmc/articles/PMC9228085/ /pubmed/35745825 http://dx.doi.org/10.3390/pharmaceutics14061253 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Cheng-Han
Hoang, Le Ngoc
Lin, Chun Che
Pan, Liang-Chen
Wu, Chiao-Li
Lin, I-Chan
Wang, Peng-Yuan
Tseng, Ching-Li
Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title_full Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title_fullStr Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title_full_unstemmed Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title_short Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
title_sort evaluation of topical and subconjunctival injection of hyaluronic acid-coated nanoparticles for drug delivery to posterior eye
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228085/
https://www.ncbi.nlm.nih.gov/pubmed/35745825
http://dx.doi.org/10.3390/pharmaceutics14061253
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