In vitro and in vivo Assessment of Keratose as a Novel Excipient of Paclitaxel Coated Balloons.
In vitro and in vivo Assessment of Keratose as a Novel Excipient of Paclitaxel Coated Balloons.
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DOI：
10.3389/fphar.2018.00808
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发表时间：
2018
影响因子：
5.6
通讯作者：
Yazdani SK
中科院分区：
文献类型：
--
作者：
Turner E;Erwin M;Atigh M;Christians U;Saul JM;Yazdani SK
目的：由于涂层技术的进步和更有效的辅料，药物涂层球囊（DCB）不断改进。目前DCB的药物选择Paclitazone是一种微管稳定化疗剂，可抑制平滑肌细胞增殖。赋形剂的作用是促进涂层稳定性并促进紫杉醇转移和保留在靶病变处，尽管目前的赋形剂缺乏持续的、长期的紫杉醇保留。角蛋白是一种天然来源的蛋白质，具有独特的性质，可以调节各种治疗药物的释放。然而，人们对其支持紫杉醇等抗增殖药物递送的能力知之甚少。本项目的目的是证明角蛋白作为DCB涂层辅料促进紫杉醇释放和递送的可行性。研究方法：将紫杉醇与角质素体外复合，分别采用高效液相色谱-质谱联用仪（HPLC-MS）和分光光度法研究紫杉醇和角质素的体外释药动力学。开发了一种定制涂层方法，通过空气喷涂方法将角质素和紫杉醇存款在市售血管成形术球囊上。涂层，然后在扫描电子显微镜下可视化和药物负载定量HPLC-MS。急性动脉转移紫杉醇在1小时进行了评估，使用一种新的离体模型，并进一步评估在体内的猪髂股损伤模型。结果：紫杉醇在体外的释放量与角质素浓度呈可调关系。通过空气喷雾涂覆的DCB产生4.0 ± 0.70 μg/mm 2的一致载药量。在扫描电子显微镜下，角蛋白-紫杉醇DCB显示出均匀的覆盖，具有一致的纹理外观。在离体1 h时，角蛋白-紫杉醇DCB的急性药物转移为43.60 ± 14.8 ng/mg。这些测量结果在体内得到进一步证实，因为急性1小时动脉紫杉醇水平为56.60 ± 66.4 ng/mg。结论：角蛋白-紫杉醇涂层DCB表现出紫杉醇摄取，并达到急性治疗动脉组织水平，证实了角蛋白作为DCB新型辅料的可行性。
Purpose: Drug coated balloons (DCB) are continually improving due to advances in coating techniques and more effective excipients. Paclitaxel, the current drug choice of DCB, is a microtubule-stabilizing chemotherapeutic agent that inhibits smooth muscle cell proliferation. Excipients work to promote coating stability and facilitate paclitaxel transfer and retention at the target lesion, although current excipients lack sustained, long-term paclitaxel retention. Keratose, a naturally derived protein, has exhibited unique properties allowing for tuned release of various therapeutic agents. However, little is known regarding its ability to support delivery of anti-proliferative agents such as paclitaxel. The goal of this project was to thus demonstrate the feasibility of keratose as a DCB-coating excipient to promote the release and delivery of paclitaxel. Methods: Keratose was combined with paclitaxel in vitro and the release kinetics of paclitaxel and keratose were evaluated through high performance liquid chromatograph-mass spectroscopy (HPLC-MS) and spectrophotometry, respectively. A custom coating method was developed to deposit keratose and paclitaxel on commercially available angioplasty balloons via an air spraying method. Coatings were then visualized under scanning electron microscopy and drug load quantified by HPLC-MS. Acute arterial transfer of paclitaxel at 1 h was assessed using a novel ex vivo model and further evaluated in vivo in a porcine ilio-femoral injury model. Results: Keratose demonstrated tunable release of paclitaxel as a function of keratose concentration in vitro. DCB coated via air spraying yielded consistent drug loading of 4.0 ± 0.70 μg/mm2. Under scanning electron microscopy, the keratose-paclitaxel DCB showed uniform coverage with a consistent, textured appearance. The acute drug transfer of the keratose-paclitaxel DCB was 43.60 ± 14.8 ng/mg at 1 h ex vivo. These measurements were further confirmed in vivo as the acute 1 h arterial paclitaxel levels were 56.60 ± 66.4 ng/mg. Conclusion: The keratose-paclitaxel coated DCB exhibited paclitaxel uptake and achieved acute therapeutic arterial tissue levels, confirming the feasibility of keratose as a novel excipient for DCB.
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影响因子：
168.9
作者：
Daemen, Joost;Wenaweser, Peter;Serruys, Patrick W.
通讯作者：
Serruys, Patrick W.
影响因子：
4.9
作者：
Dias, George J.;Peplow, Philip V.;Kelly, Robert J.
通讯作者：
Kelly, Robert J.
影响因子：
11.3
作者：
Gongora, Carlos A.;Shibuya, Masahiko;Granada, Juan F.
通讯作者：
Granada, Juan F.
DOI：
10.1002/jbm.b.31251
发表时间：
2009-07-01
影响因子：
3.4
作者：
Aboushwareb, Tamer;Eberli, Daniel;Van Dyke, Mark
通讯作者：
Van Dyke, Mark
影响因子：
5.7
作者：
Cortese, Bernardo;Micheli, Andrea;Limbruno, Ugo
通讯作者：
Limbruno, Ugo