Studies of biodegradable drug-eluting tracheal stents.
Ng, Anthony Herr Cheun.
Date of Issue2012
School of Materials Science and Engineering
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.