Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib
Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib
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DOI：
10.1016/j.biomaterials.2013.08.090
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发表时间：
2013-12-01
期刊：
影响因子：
14
通讯作者：
Solzbacher, Florian
中科院分区：
文献类型：
--
作者：
Avula, Mahender Nath;Rao, Archana Nagaraja;Solzbacher, Florian
宿主异物反应（FBR）对许多植入生物材料的性能产生不利影响，特别是生物传感器，包括临床流行的血糖监测传感器。在植入的传感器周围纤维囊的反应性形成阻碍了必需分析物从周围组织向传感器的运输，导致葡萄糖反应敏感性的丧失和最终的传感器故障。有几种策略试图通过使用局部递送药物和生物分子来减轻异物反应对CGM传感器的影响，但收效甚微。本研究描述了酪氨酸激酶抑制剂masitinib从传感器植入物释放到靶组织肥大细胞作为FBR的关键介质。模型植入物涂有一种复合聚合物亲水性基质，该基质在组织植入时迅速溶解，沉积含有马西替尼的降解较慢的聚合物微粒。基质溶解限制了涂层对传感器功能的干扰，同时建立了局部控释给药库配方，以改变植入物组织药理学和解决FBR问题。在小鼠皮下口袋植入物模型中评价药物疗效。药物在体外释放时间超过30天。通过14、21和28天的种植体囊膜厚度和炎症细胞密度评估的体内FBR结果显示，与对照种植体部位相比，马西替尼释放种植体部位周围的囊膜厚度有统计学意义上的显著减少。(C) 2013 Elsevier Ltd.版权所有。
The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success. This study describes release of a tyrosine kinase inhibitor - masitinib - from the sensor implant to target tissue resident mast cells as key mediators of the FBR. Model implants are coated with a composite polymer hydrophilic matrix that rapidly dissolves upon tissue implantation to deposit slower-degrading polymer microparticles containing masitinib. Matrix dissolution limits coating interference with sensor function while establishing a local controlled-release delivery depot formulation to alter implant tissue pharmacology and addressing the FBR. Drug efficacy was evaluated in a murine subcutaneous pocket implant model. Drug release extends to more than 30 days in vitro. The resulting FBR in vivo, evaluated by implant capsule thickness and inflammatory cell densities at 14, 21, and 28 days, displays statistically significant reduction in capsule thickness around masitinib-releasing implant sites compared to control implant sites. (C) 2013 Elsevier Ltd. All rights reserved.