A novel photodynamic therapy-based drug delivery system layered on a stent for treating cholangiocarcinoma

  • Po-Chin Liang
  • Kai-Wen Huang
  • Chien-Chih Tung
  • Ming-Chu Chang
  • Fuh-Yu Chang
  • Jau-Min Wong
  • Yu-Ting Chang


This study aimed to investigate the drug delivery efficacy and bio-effectiveness of a novel photodynamic therapy (PDT)-matrix drug delivery system for cholangiocarcinoma (CCA). Metallic stents were coated with polyurethane (PU) as the first layer. A 2-hydroxyethyl methacrylate (2-HEMA)/ethylene glycol dimethacrylate (EGDMA)/benzoyl peroxide (BPO) layer and a poly(ethylene-co-vinyl acetate) (PEVA)/poly(n-butyl methacrylate) (PBMA)/polyvinylpyrrolidone K30 (K30) layer containing various concentrations of Photofrin were then incorporated onto the stent as the second and third layers. After incubating the layered membranes with cultured CCA cell line, the release of Photofrin, cell viability, the intracellular uptake of Photofrin, reactive oxygen species (ROS) generation, and apoptosis were determined. Using a single-layer diffusion model, the maximum release of Photofrin from the 5 to 10% K30 formulas was 80 and 100%, respectively, after 24 h. When using the multiple-layer diffusion model, the released Photofrin showed an initial burst of the loading dose from the PEVA/PBMA/K30 layer. In the immobilized model, less than 5% of the Photofrin from the 2-HEMA/EGDMA/BPO layer was released over the 24-h period. Cell viability decreased linearly with increasing Photofrin concentrations, and ROS generation and apoptosis were shown to increase significantly with increasing Photofrin concentrations, until the concentration of Photofrin reached a saturation point of 1.5 μg/ml. This new, multiple-layered, PDT-based stent with dual-release mechanisms is a promising treatment for CCA and cancer-related ductal stenosis.


Photodynamic therapy (PDT) Stent Cholangiocarcinoma 



2-hydroxyethyl methacrylate


Benzoyl peroxide




Drug delivery system


Drug-eluting stent


Ethylene glycol dimethacrylate


Polyvinylpyrrolidone K30


Poly(n-butyl methacrylate)


Photodynamic therapy


Poly(ethylene-co-vinyl acetate)


Reactive oxygen species



This study was supported by the National Research Program for Biopharmaceuticals (NRPB), Republic of China (R.O.C.), Taiwan (Project No. 100INP015-1 and 100INP015-2). The stent used in this study was provided by Professor Fuh-Yu Chang, Department of Mechanical Engineering, National Taiwan University of Science and Technology.

Compliance with ethical standards

Conflict of interest

The authors declare no financial or commercial conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Po-Chin Liang
    • 1
  • Kai-Wen Huang
    • 2
  • Chien-Chih Tung
    • 3
  • Ming-Chu Chang
    • 4
  • Fuh-Yu Chang
    • 5
  • Jau-Min Wong
    • 4
  • Yu-Ting Chang
    • 4
  1. 1.Department of Medical Imaging National Taiwan University Hospital, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of Integrated Diagnostics & Therapeutics and Internal Medicine, National Taiwan University Hospital, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  4. 4.Department of Internal Medicine, National Taiwan University Hospital, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  5. 5.Department of Mechanical EngineeringNational Taiwan University of Science and TechnologyTaipeiTaiwan

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