Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control.
Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control.
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DOI：
10.1089/dia.2004.6.887
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Burgess, Diane J
中科院分区：
文献类型：
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作者：
Patil, Siddhesh D;Papadimitrakopoulos, Fotios;Burgess, Diane J
背景：用于代谢监测的植入式葡萄糖生物传感器的成功性能取决于组织相容性。由于透析诱导的组织损伤和此类传感器的长期存在而发生的阴性免疫刺激组织反应可导致功能丧失和器械故障。使用新型的聚（乳酸-羟基乙酸）（PLGA）微球/聚（乙烯醇）（PVA）水凝胶复合涂层的植入式生物传感器，以控制局部炎症和纤维化的传感器/组织interface.METHODS：地塞米松载PLGA微球制备使用溶剂蒸发技术。通过将微球分散在PVA溶液中并进行冻融循环来制备复合材料。将复合材料植入大鼠皮下组织。体外和体内药物释放动力学进行了研究。免疫刺激反应通过组织病理学评价确定切除tissue.Results：PLGA微球/PVA水凝胶复合材料实现了局部地塞米松交付近似零级释放动力学。观察到体外-体内线性水平A相关性（R2 = 0.97）。地塞米松以0.17微克/天的稳定速率释放足以控制急性和慢性炎症以及纤维化。植入不含药物的复合材料导致植入部位的炎症介导细胞显著浸润，这是急性炎症的特征，随后在第3周植入物周围纤维化带增殖。洗脱地塞米松的PLGA微球/PVA水凝胶复合材料通过降低炎症水平成功地控制了传感器-组织界面处的负组织反应。在正常组织中观察到的那些。这些复合材料显示出作为可植入生物传感器的涂层以改善生物相容性和延长传感器寿命的前景。
BACKGROUND: Successful performance of implantable glucose biosensors for metabolic monitoring is dependent on tissue compatibility. Negative immunostimulatory tissue reactions that occur due to implantation-induced tissue injury and the prolonged presence of such sensors can lead to a loss of functionality and device failure. The use of novel poly(lactic-co-glycolic) acid (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composite coatings for implantable biosensors to control localized inflammation and fibrosis at the sensor/tissue interface is reported.METHODS: Dexamethasone-loaded PLGA microspheres were prepared using a solvent evaporation technique. Composites were fabricated by dispersing microspheres in PVA solution and performing freeze-thaw cycling. Composites were implanted into subcutaneous tissue of rats. In vitro and in vivo drug release kinetics were studied. Immunostimulatory response was determined through histopathological evaluation of excised tissue.RESULTS: PLGA microsphere/PVA hydrogel composites achieved localized dexamethasone delivery with approximate zero-order release kinetics. A linear level A in vitro-in vivo correlation was observed (R2 = 0.97). Dexamethasone released at a steady rate of 0.17 microg/day was sufficient to control acute and chronic inflammation as well as fibrosis. Implantation of composites containing no drug led to significant infiltration of inflammation-mediating cells at the implant site characteristic of acute inflammation followed by proliferation of a fibrotic band surrounding the implant by week 3.CONCLUSIONS: PLGA microsphere/PVA hydrogel composites eluting dexamethasone were successful in controlling negative tissue reactions at the sensor-tissue interface by reducing the level of inflammation-mediation cells to those observed in normal tissue. These composites show promise as coatings for implantable biosensors to improve biocompatibility and prolong sensor lifetime.