Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

Abstract

Background:Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug.Methods:Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent.Results:Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect.Conclusions:The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.

Engineering an immunomodulatory drug-eluting stent to treat laryngotracheal stenosis

“…This is the first time, to our knowledge, a PLLA-PCL tracheal stent was deployed in a mouse model. Although other materials were used in studies with rabbit and canine models [26,27,28] , PLLA-PCL chosen for this study because it causes little inflammation in the native tissue [29] . Moreover, the rabbit and canine models used in the past do not use the LTS disease model to test the effects of a DES.…”

A Design-Based Stereologic Method to Quantify the Tissue Changes Associated with a Novel Drug-Eluting Tracheobronchial Stent

“…This delivery system, which combines a stent with a gelatin gel, can be modified easily and could be used to deliver other substances at high local concentrations to the tissues surrounding the stent. One potential application could be the delivery of agents that affect granulation tissue formation, for example mitomycin [37-43], which might be useful in preventing the buildup of granulation tissue. This strategy could also be used to deliver compounds that stimulate the immune response against malignant tumors infiltrating the airways [16].…”

Effects of Paclitaxel-conjugated N-Succinyl-Hydroxyethyl Chitosan Film for Proliferative Cholangitis in Rabbit Biliary Stricture Model

“…Previous studies showed that PTX, an antineoplastic agent, could reduce the development of PC and subsequent bile duct stricture. [ 14 15 ] Unfortunately, poor solubility has limited its clinical usage. [ 16 ] In the last few years, great efforts have been made for development of new delivery systems for PTX, such as polymer conjugates, liposomes, polymeric micelles, parenteral emulsions, polymeric micro/nanoparticles, and water-soluble prodrugs.…”