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Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis

In this study, we fabricated a doxycycline (doxy)-eluting nanofiber-covered endotracheal stent for the prevention of stent intubation-related tissue fibrosis and re-stenosis. The nanofiber was deposited directly on the outer surface of the stent using a coaxial electrospinning method to form a doxy-...

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Autores principales: Baskaran, Rengarajan, Ko, Un-Jeong, Davaa, Enkhzaya, Park, Ji Eun, Jiang, Yixin, Lee, Junghan, Yang, Su-Geun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723391/
https://www.ncbi.nlm.nih.gov/pubmed/31430987
http://dx.doi.org/10.3390/pharmaceutics11080421
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author Baskaran, Rengarajan
Ko, Un-Jeong
Davaa, Enkhzaya
Park, Ji Eun
Jiang, Yixin
Lee, Junghan
Yang, Su-Geun
author_facet Baskaran, Rengarajan
Ko, Un-Jeong
Davaa, Enkhzaya
Park, Ji Eun
Jiang, Yixin
Lee, Junghan
Yang, Su-Geun
author_sort Baskaran, Rengarajan
collection PubMed
description In this study, we fabricated a doxycycline (doxy)-eluting nanofiber-covered endotracheal stent for the prevention of stent intubation-related tissue fibrosis and re-stenosis. The nanofiber was deposited directly on the outer surface of the stent using a coaxial electrospinning method to form a doxy-eluting cover sleeve. Poly(d,l-lactide) was used as the shell-forming polymer and dedicated drug release-control membrane. Polyurethane was selected as the drug-loading core polymer. The compositional ratio of the core to shell was adjusted to 1:0, 1:2, and 1:4 by changing the electro-spray rate of each polymeric solution and microscopic observation of nanofibers using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and the fluorescence microscopy proved core-shell structure of nanofibers. The in vitro release study suggested that the release of doxy could be controlled by increasing the compositional ratio of the shell. The growth of HT1080 fibrosarcoma cells was inhibited by the 10% doxy-containing nanofiber. The real-time polymerase chain reaction (PCR) in HT1080 cells and xenografted tissue models indicated that the doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9). Overall, our study demonstrates that a doxy-eluting core-shell nanofiber stent can be successfully fabricated using coaxial electrospinning and displays the potential to prevent fibrotic re-stenosis, which is the most problematic clinical complication of tracheal stent intubation.
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spelling pubmed-67233912019-09-10 Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis Baskaran, Rengarajan Ko, Un-Jeong Davaa, Enkhzaya Park, Ji Eun Jiang, Yixin Lee, Junghan Yang, Su-Geun Pharmaceutics Article In this study, we fabricated a doxycycline (doxy)-eluting nanofiber-covered endotracheal stent for the prevention of stent intubation-related tissue fibrosis and re-stenosis. The nanofiber was deposited directly on the outer surface of the stent using a coaxial electrospinning method to form a doxy-eluting cover sleeve. Poly(d,l-lactide) was used as the shell-forming polymer and dedicated drug release-control membrane. Polyurethane was selected as the drug-loading core polymer. The compositional ratio of the core to shell was adjusted to 1:0, 1:2, and 1:4 by changing the electro-spray rate of each polymeric solution and microscopic observation of nanofibers using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and the fluorescence microscopy proved core-shell structure of nanofibers. The in vitro release study suggested that the release of doxy could be controlled by increasing the compositional ratio of the shell. The growth of HT1080 fibrosarcoma cells was inhibited by the 10% doxy-containing nanofiber. The real-time polymerase chain reaction (PCR) in HT1080 cells and xenografted tissue models indicated that the doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9). Overall, our study demonstrates that a doxy-eluting core-shell nanofiber stent can be successfully fabricated using coaxial electrospinning and displays the potential to prevent fibrotic re-stenosis, which is the most problematic clinical complication of tracheal stent intubation. MDPI 2019-08-19 /pmc/articles/PMC6723391/ /pubmed/31430987 http://dx.doi.org/10.3390/pharmaceutics11080421 Text en © 2019 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
Baskaran, Rengarajan
Ko, Un-Jeong
Davaa, Enkhzaya
Park, Ji Eun
Jiang, Yixin
Lee, Junghan
Yang, Su-Geun
Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title_full Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title_fullStr Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title_full_unstemmed Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title_short Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis
title_sort doxycycline-eluting core-shell type nanofiber-covered trachea stent for inhibition of cellular metalloproteinase and its related fibrotic stenosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723391/
https://www.ncbi.nlm.nih.gov/pubmed/31430987
http://dx.doi.org/10.3390/pharmaceutics11080421
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