Design of a photocleavable drug binding platform for a novel remotely controllable drug coated balloon
Design of a photocleavable drug binding platform for a novel remotely controllable drug coated balloon
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DOI：
10.1016/j.jddst.2021.102375
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发表时间：
2021-02-15
影响因子：
5
通讯作者：
Akagi, Yuki
中科院分区：
文献类型：
--
作者：
Mizuno, Hayato Laurence;Anraku, Yasutaka;Akagi, Yuki
药物涂层球囊已成为治疗冠状动脉狭窄的常规器械（如药物洗脱支架）的替代品。然而，还没有开发出将足够的药物递送到病变的涂层方法。为了提高递送效率-通过减少血流下的药物洗脱和增加从球囊表面到动脉壁的转移，我们提出了一种光可裂解的药物结合平台，其将药物牢固地结合到球囊表面上，并在由光照射触发的狭窄部位释放。作为概念证明，我们通过将3-氨基-3-（2-硝基-苯基）丙酸（ANP）缀合到Cy 5（模型药物）上，然后将其缀合到乳胶珠上来设计模型系统，所述乳胶珠具有与用于常规球囊的材料类似的配方。我们通过照射365 nm的光来触发释放并评估细胞对Cy 5的摄取来证实其光响应性和释放效率。结果证明，所提出的平台释放Cy 5时，只有当它是由光照射触发，与药物洗脱率低至11%的传统DCB涂层在血液填充的环境。我们的体外评估表明，释放的物质保持功能，并按设计进入细胞。所提出的概念可以提供一种通过各种管腔样组织的高效远程可控局部药物递送的方法。
Drug coated balloons have been emerging as alternatives to conventional devices such as drug eluting stents in the treatment of coronary artery stenosis. However, no coating method has been developed to deliver sufficient drug to the lesion. To enhance delivery efficiency- both by reducing the drug wash off under bloodstream and increasing transfer from balloon surface to the arterial wall, we have proposed a photocleavable drug binding platform, which securely bonds the drugs onto the balloon surface, and releases at the site of stenosis triggered by photoirradiation. As a proof of concept, we designed a model system by conjugating 3-amino-3-(2-nitro-phenyl) propionic acid (ANP) onto Cy5, the model drug, then conjugating this onto latex beads, which has a formulation similar to the materials used for conventional balloons. We confirmed its photoresponsivity and release efficiency by irradiating 365 nm light to trigger release and evaluated cellular uptake of Cy5 in vitro. Results proved that the proposed platform releases Cy5 when, and only when, it is triggered by photoirradiation, with drug wash off rate as low as 11% of the conventional DCB coatings in blood-filled environment. Our in vitro evaluation showed that the released substance remains functional and enters cells as designed. The proposed concept may provide a method of highly efficient remotely controllable topical drug delivery through various lumen-like tissues.