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

Baskaran Baskaran,Ko Ko,Davaa Davaa,Yang Yang,Jiang Jiang,Park Park,Lee Lee

doi:10.3390/pharmaceutics11080421

Abstract

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.

Highlights

Tracheal intubation is the placement of a conduit into the trachea to prevent airway obstruction [1,2,3]
We successfully developed a doxy-eluting core-shell nanofiber for the prevention of fibrosis, which frequently occurs after trachea stent intubation
Morphology characterization using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescence imaging indicated the successful formation of a core-shell structured nanofiber

Summary

Introduction

Tracheal intubation is the placement of a conduit into the trachea to prevent airway obstruction [1,2,3]. Tracheal intubation is performed on patients during emergency situations such as respiratory failure, stroke, and coma in the clinic [4,5,6]. The trachea stent itself induces re-stenosis accompanied by granulomatosis from stent-induced inflammation and tissue damage [7]. Stent-induced inflammation causes infection, the development of tissue fibrosis, the formation of granulomatous tissues, and eventually the narrowing of the trachea duct, leading to stenosis [8,9,10]. Resection of over-grown tissues can be performed as a palliative treatment for patients. There is a lack of medical or surgical options to prevent stent-induced tissue fibrosis

Methods

Results

Conclusion