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Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery
Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF)...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698121/ https://www.ncbi.nlm.nih.gov/pubmed/33182620 http://dx.doi.org/10.3390/pharmaceutics12111072 |
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author | Gote, Vrinda Mandal, Abhirup Alshamrani, Meshal Pal, Dhananjay |
author_facet | Gote, Vrinda Mandal, Abhirup Alshamrani, Meshal Pal, Dhananjay |
author_sort | Gote, Vrinda |
collection | PubMed |
description | Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1β and TNF-α after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD. |
format | Online Article Text |
id | pubmed-7698121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76981212020-11-29 Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery Gote, Vrinda Mandal, Abhirup Alshamrani, Meshal Pal, Dhananjay Pharmaceutics Article Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1β and TNF-α after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD. MDPI 2020-11-10 /pmc/articles/PMC7698121/ /pubmed/33182620 http://dx.doi.org/10.3390/pharmaceutics12111072 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gote, Vrinda Mandal, Abhirup Alshamrani, Meshal Pal, Dhananjay Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title | Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title_full | Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title_fullStr | Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title_full_unstemmed | Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title_short | Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery |
title_sort | self-assembling tacrolimus nanomicelles for retinal drug delivery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698121/ https://www.ncbi.nlm.nih.gov/pubmed/33182620 http://dx.doi.org/10.3390/pharmaceutics12111072 |
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