Liang Po-Chin, Huang Kai-Wen, Tung Chien-Chih, Chang Ming-Chu, Chang Fuh-Yu, Wong Jau-Min, Chang Yu-Ting
Department of Medical Imaging National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Biomed Microdevices. 2017 Nov 22;20(1):3. doi: 10.1007/s10544-017-0249-1.
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.
本研究旨在探究一种用于胆管癌（CCA）的新型光动力疗法（PDT）-基质药物递送系统的药物递送效果和生物有效性。金属支架首先涂覆聚氨酯（PU）作为第一层。然后将含有不同浓度光敏剂的甲基丙烯酸-2-羟乙酯（2-HEMA）/二甲基丙烯酸乙二醇酯（EGDMA）/过氧化苯甲酰（BPO）层以及聚乙烯-醋酸乙烯酯共聚物（PEVA）/聚甲基丙烯酸正丁酯（PBMA）/聚乙烯吡咯烷酮K30（K30）层作为第二层和第三层加入到支架上。将分层膜与培养的CCA细胞系孵育后，测定光敏剂的释放、细胞活力、光敏剂的细胞内摄取、活性氧（ROS）生成以及细胞凋亡情况。使用单层扩散模型，在24小时后，5%至10% K30配方中光敏剂的最大释放率分别为80%和100%。当使用多层扩散模型时，释放的光敏剂显示出从PEVA/PBMA/K30层有一个初始的加载剂量突释。在固定模型中，24小时内来自2-HEMA/EGDMA/BPO层的光敏剂释放量不到5%。细胞活力随光敏剂浓度增加呈线性下降，并且ROS生成和细胞凋亡随光敏剂浓度增加而显著增加，直到光敏剂浓度达到1.5μg/ml的饱和点。这种具有双释放机制的新型多层基于PDT的支架是治疗CCA和癌症相关导管狭窄的一种有前景的疗法。
