Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using electrospinning

Abstract

BackgroundThe combination of biliary stent with photodynamic and chemotherapy seemed to be a beneficial palliative treatment of unresectable cholangiocarcinoma. However, by intravenous delivery to the target tumor the distribution of the drug had its limitations and caused serious side effect on non-target organs. Therefore, in this study, we are going to develop a localized eluting stent, named PDT-chemo stent, covered with gemcitabine (GEM) and hematoporphyrin (HP).MethodsThe prototype of PDT-chemo stent was made through electrospinning and electrospraying dual-processes with an electrical charge to cover the stent with a drug-storing membrane from polymer liquid. The design of prototype used PU as the material of the backing layer, and PCL/PEG blends in different molar ratio of 9:1 and of 1:4 were used in two drug-storing layers with GEM and HP loaded respectively.ResultsThe optical microscopy revealed that the backing layer was formed in fine fibers from electrospinning, while drug-storing layers, attributed to the droplets from electrospraying process. The covered membrane, the morphology of which was observed by scanning electron microscopy (SEM), covered the stent surface homogeneously without crack appearances. The GEM had almost 100% of electrosprayed efficiency than 70% HP loaded on the covered membrane due to the different solubility of drug in PEG/PCL blends. Drug release study confirmed the two-phased drug release pattern by regulating in different molar ratio of PEG/PCL blends polymer.ConclusionsThe result proves that the PDT-chemo stent is composed of a first burst-releasing phase from HP and a later slow-releasing phase from GEM eluting. This two-phase of drug eluting stent may provide a new prospect of localized and controlled release treatment for cholangiocarcinoma disease.

Controlled NO-Release from 3D-Printed Small-Diameter Vascular Grafts Prevents Platelet Activation and Bacterial Infectivity

“…Our results verify that the amount of NO released from the grafts is capable to eradicate all E. coli and S. epidermidis before 24 h and 99.99% of S. aureus before 24 h. Together, this means that the bacterial load was reduced by 4 orders of magnitude and S. aureus even by 100% before 48 h, while bacteria were proliferating without any growth limitation in the presence of control grafts. This initial protection, as previously reached by drug diluting stents, 49 is therefore likely a concept relevant for vascular grafts.…”

“…They explained that the hydrophilic PEG in PEG-PCL blends makes the aqueous phase and work as a pore former, which corresponds to formation of swollen portions with controlled drug releasing kinetics. 49 This gave us the idea to create the new coating with a PEG-PCL matrix for controlled NO release. We hypothesized that PEG, as a very hydrophilic polymer, can absorb water into the polymeric matrix facilitating the dissolution of the NO donor.…”

“…Recently, Chen et al used PEG (Mw = 20 000) and PCL (Mw = 80 000) blends with various molar ratios (PEG/PCL = 1–9 and 4–1) to construct drug eluting stents using electrospinning and electrospraying techniques. They explained that the hydrophilic PEG in PEG-PCL blends makes the aqueous phase and work as a pore former, which corresponds to formation of swollen portions with controlled drug releasing kinetics . This gave us the idea to create the new coating with a PEG-PCL matrix for controlled NO release.…”

A review on biodegradable biliary stents: materials and future trends

“…PCL is used mainly as the coating material for metallic or PDX biliary stents [ 36 , [77] , [78] , [79] ]. Chang et al studied the in vitro degradation behavior of PCL film in bile.…”

Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR

“…PDT has been reported to be used upon skin lesions or hollow organ walls, and in recent years more attention has been paid to its potential in the treatment of solid organ lesions and digestive tract dysplasia and early cancerous lesions (Evrard et al, 1991;Schuitmaker et al, 1996;Bown et al, 2002), including cholangiocarcinoma (Kahaleh, 2012;McCaughan et al, 1991;Talreja et al, 2011). Although the synergetic anti-tumor effects of PDT/gemcitabine combination have been reported within cholangiocarcinoma (Chen et al, 2014;Hong et al, 2014;Wentrup et al, 2016;Kim et al, 2018), the mechanism underlying the synergetic anticancer effect remains unclear.…”