Studies of biodegradable drug-eluting tracheal stents

A fully biodegradable tracheal stent to prevent occlusion and collapse of the human airway, due to both conditions of tracheal stenosis and tracheomalacia, is an ideal treatment with several advantages. The most important of which are the removal for the need of a second surgical intervention to rem...

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Main Author: Ng, Anthony Herr Cheun
Other Authors: Subbu S. Venkatraman
Format: Theses and Dissertations
Language:English
Published: 2012
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Online Access:https://hdl.handle.net/10356/50609
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-506092023-03-04T16:38:55Z Studies of biodegradable drug-eluting tracheal stents Ng, Anthony Herr Cheun Subbu S. Venkatraman School of Materials Science & Engineering DRNTU::Engineering::Bioengineering DRNTU::Engineering::Materials::Biomaterials A fully biodegradable tracheal stent to prevent occlusion and collapse of the human airway, due to both conditions of tracheal stenosis and tracheomalacia, is an ideal treatment with several advantages. The most important of which are the removal for the need of a second surgical intervention to remove an implanted stent, and the potential for drug-elution from biodegradable stent matrices. Currently, there is insufficient understanding of the performance of fully biodegradable, drug-eluting tracheal stents, both in-vitro and in-vivo. To achieve better understanding, this project attempted to develop a physical model to study the degradation phenomena of biodegradable polymers under a simulated tracheal environment. In-vitro drug-release studies conducted in a simulated tracheal condition were also performed. Results from these in-vitro studies finally led to the development of prototypical biodegradable tracheal stents that were implanted in rabbits and observed. Correlations between in-vitro and invivo performance of such stents were attempted at the end. It was realised that well-studied bulk-degrading polymers do have the possibility of exhibiting pseudo “surface-eroding” phenomenon when exposed to the unique conditions in the tracheal passage. The addition of certain plasticizers also affects the degradation kinetics of biodegradable polymers in such environments. These observations led to the selection of a candidate material for the fabrication of stents for the animal study. The drug of interest, mitomycin C (MMC), was studied in relation to its stability in physiological conditions and elution phenomena from a polymer under tracheal environments. The saturation concentration and diffusion coefficient for MMC in the polymer were elucidated. Attempts to model its release phenomena using currently accepted principles required better understanding of the polymer-drug system and a methodology to correct release results due to MMC instability at longer elution periods. Lastly, the results from two animal studies suggest that even though the stent material was well-tolerated in the trachea, MMC had to be eluted at efficacious doses for longer time periods. Formulations of MMC both incorporated into the stent body and spray-coated on the outer surface did not inhibit late-stage tracheal restenosis in rabbits. More studies into stabilising MMC and preventing too early drug-depletion was concluded to be the way forward for such a novel fully biodegradable tracheal stent to be in useful service. DOCTOR OF PHILOSOPHY (MSE) 2012-07-27T01:21:51Z 2012-07-27T01:21:51Z 2012 2012 Thesis Ng, A. H. C. (2012). Studies of biodegradable drug-eluting tracheal stents. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/50609 10.32657/10356/50609 en 168 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Engineering::Bioengineering
DRNTU::Engineering::Materials::Biomaterials
spellingShingle DRNTU::Engineering::Bioengineering
DRNTU::Engineering::Materials::Biomaterials
Ng, Anthony Herr Cheun
Studies of biodegradable drug-eluting tracheal stents
description A fully biodegradable tracheal stent to prevent occlusion and collapse of the human airway, due to both conditions of tracheal stenosis and tracheomalacia, is an ideal treatment with several advantages. The most important of which are the removal for the need of a second surgical intervention to remove an implanted stent, and the potential for drug-elution from biodegradable stent matrices. Currently, there is insufficient understanding of the performance of fully biodegradable, drug-eluting tracheal stents, both in-vitro and in-vivo. To achieve better understanding, this project attempted to develop a physical model to study the degradation phenomena of biodegradable polymers under a simulated tracheal environment. In-vitro drug-release studies conducted in a simulated tracheal condition were also performed. Results from these in-vitro studies finally led to the development of prototypical biodegradable tracheal stents that were implanted in rabbits and observed. Correlations between in-vitro and invivo performance of such stents were attempted at the end. It was realised that well-studied bulk-degrading polymers do have the possibility of exhibiting pseudo “surface-eroding” phenomenon when exposed to the unique conditions in the tracheal passage. The addition of certain plasticizers also affects the degradation kinetics of biodegradable polymers in such environments. These observations led to the selection of a candidate material for the fabrication of stents for the animal study. The drug of interest, mitomycin C (MMC), was studied in relation to its stability in physiological conditions and elution phenomena from a polymer under tracheal environments. The saturation concentration and diffusion coefficient for MMC in the polymer were elucidated. Attempts to model its release phenomena using currently accepted principles required better understanding of the polymer-drug system and a methodology to correct release results due to MMC instability at longer elution periods. Lastly, the results from two animal studies suggest that even though the stent material was well-tolerated in the trachea, MMC had to be eluted at efficacious doses for longer time periods. Formulations of MMC both incorporated into the stent body and spray-coated on the outer surface did not inhibit late-stage tracheal restenosis in rabbits. More studies into stabilising MMC and preventing too early drug-depletion was concluded to be the way forward for such a novel fully biodegradable tracheal stent to be in useful service.
author2 Subbu S. Venkatraman
author_facet Subbu S. Venkatraman
Ng, Anthony Herr Cheun
format Theses and Dissertations
author Ng, Anthony Herr Cheun
author_sort Ng, Anthony Herr Cheun
title Studies of biodegradable drug-eluting tracheal stents
title_short Studies of biodegradable drug-eluting tracheal stents
title_full Studies of biodegradable drug-eluting tracheal stents
title_fullStr Studies of biodegradable drug-eluting tracheal stents
title_full_unstemmed Studies of biodegradable drug-eluting tracheal stents
title_sort studies of biodegradable drug-eluting tracheal stents
publishDate 2012
url https://hdl.handle.net/10356/50609
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