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

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Abstract

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.

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Abbreviations

2-HEMA:

2-hydroxyethyl methacrylate

BPO:

Benzoyl peroxide

CCA:

Cholangiocarcinoma

DDS:

Drug delivery system

DES:

Drug-eluting stent

EGDMA:

Ethylene glycol dimethacrylate

K30:

Polyvinylpyrrolidone K30

PBMA:

Poly(n-butyl methacrylate)

PDT:

Photodynamic therapy

PEVA:

Poly(ethylene-co-vinyl acetate)

ROS:

Reactive oxygen species

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Medical Imaging National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Po-Chin Liang

  2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    Kai-Wen Huang

  3. Department of Integrated Diagnostics & Therapeutics and Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chien-Chih Tung

  4. Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ming-Chu Chang, Jau-Min Wong & Yu-Ting Chang

  5. Department of Mechanical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan

    Fuh-Yu Chang

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  1. Po-Chin Liang
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  2. Kai-Wen Huang
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  3. Chien-Chih Tung
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  4. Ming-Chu Chang
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  5. Fuh-Yu Chang
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Correspondence to Yu-Ting Chang.

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Liang, PC., Huang, KW., Tung, CC. et al. A novel photodynamic therapy-based drug delivery system layered on a stent for treating cholangiocarcinoma. Biomed Microdevices 20, 3 (2018). https://doi.org/10.1007/s10544-017-0249-1

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  • DOI: https://doi.org/10.1007/s10544-017-0249-1

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