Zero-order release of 5-fluorouracil from PCL-based films featuring trilayered structures for stent application.
Zero-order release of 5-fluorouracil from PCL-based films featuring trilayered structures for stent application.
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DOI：
10.1016/j.ejpb.2011.01.003
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发表时间：
2011-05
期刊：
影响因子：
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通讯作者：
Lei Lei-Lei;X. Liu;Yuanyuan Shen;JieYing Liu;Mufei Tang;Zhong-min Wang;Sheng-rong Guo;Liang Cheng
中科院分区：
文献类型：
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作者：
Lei Lei-Lei;X. Liu;Yuanyuan Shen;JieYing Liu;Mufei Tang;Zhong-min Wang;Sheng-rong Guo;Liang Cheng
提出了一种具有涂层（CL）、负载有抗肿瘤药物5-氟尿嘧啶（5-FU）的药物储存层（DSL）和背衬层（BL）的基于聚（ε-己内酯）（PCL）的三层膜，用于基于膜的支架在恶性狭窄或狭窄中的应用。采用V-C扩散池研究CL的药物渗透性，采用扫描电子显微镜（SEM）观察CL的微观结构和形态。药物从三层膜中的释放呈现零级模式，释放过程遵循“由外到内”的模式。对零级释药模式的形成机理和影响因素进行了深入的阐述，并对影响释药的因素进行了考察。DSL中初始载药量的降低减缓了药物释放，并减少了零级释放模式。CL的药物渗透性显著依赖于CL厚度，但不显着对PCL分子量。此外，PEG致孔剂的加入通过提高CL的药物渗透性而加速药物释放，并通过PEG释放试验和SEM揭示了PEG的作用机理。CL中5-FU的负载可能导致两相释放曲线。该研究揭示了由于其高度可调的零级药物释放，三层膜在控制药物递送到管腔内肿瘤中的潜力。
A trilayered Poly(ε-caprolactone) (PCL)-based film with a coating layer (CL), a drug-storing layer (DSL) loaded with antitumor drug 5-Fluorouracil (5-FU) and a backing layer (BL) are presented for film-based stent application in malignant stricture or stenosis. V-C diffusion cells were used to investigate the drug permeability of the CL, while scanning electron microscopy (SEM) was employed for observing the microscopic architectures and morphologies. Drug release from the trilayered films exhibited a zero-order pattern, and the release process followed an ‘outer-to-inner’ pattern. The formation mechanism and influencing factors of the zero-order drug release pattern were in-depth elucidated, and factors affecting the drug release were also investigated. The reduction of initial drug loading in DSL slowed the drug release and diminished the zero-order release pattern. Drug permeability of the CL depended significantly on CL thickness, but not significantly on PCL molecular weight. Besides, the addition of PEG porogen in the CL accelerated the drug release by elevation of the drug permeability of CL, and the action mechanism of PEG was revealed by the PEG release test and SEM. The loading of 5-FU in the CL could lead to a two-phased release profile. This study revealed the potential of the trilayered film in controlled drug delivery to intraluminal tumor due to its highly tunable zero-order drug release.