PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation
PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation
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DOI：
10.1016/j.ijpharm.2009.09.046
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发表时间：
2010-01-15
影响因子：
5.8
通讯作者：
Burgess, Diane J.
中科院分区：
文献类型：
--
作者：
Bhardwaj, Upkar;Sura, Radhakrishana;Burgess, Diane J.
研究了地塞米松负载的PLGA微球/PVA水凝胶复合物作为植入装置的外部药物洗脱涂层以提供对异物反应的保护。制备两种微球群：25 kDa PLGA微球，其具有在30-33天内延伸的典型三相释放曲线;和75 kDa PLGA微球，其在前25天显示最小释放，然后在80-85天内增加至释放。在复合材料中掺入微球仅轻微改变释放曲线。含有25 kDa微球的复合物在30-35天内释放地塞米松，而含有等量的25和75 kDa微球的组合的复合物在90-95天内释放地塞米松。药效学研究表明，仅含有25 kDa微球的复合材料可提供1个月的炎症反应保护，然而，地塞米松耗尽后出现延迟的组织反应。这表明在整个植入物寿命期间需要持续释放抗炎剂以控制炎症并防止纤维化。使用25 kDa和75 kDa微球的组合制造的复合材料控制了90天的组织反应。在相同复合包衣中组合不同微球群体的这种策略可用于调节释放曲线以获得所需的释放程度和持续时间。这种复合材料提供了一种创新的解决方案，以控制组织-设备界面处的异物反应。(C)2009爱思唯尔有限公司版权所有。
Dexamethasone loaded PLGA microsphere/PVA hydrogel composites were investigated as an outer drug-eluting coating for implantable devices to provide protection against the foreign body response. Two populations of microspheres were prepared: 25 kDa PLGA microspheres which had a typical triphasic release profile extending over 30-33 days; and 75 kDa PLGA microspheres which showed minimal release for the first 25 days and then increased to release over 80-85 days. Incorporation of the microspheres in the composites only slightly altered the release profile. Composites containing 25 kDa microspheres released dexamethasone over 30-35 days while composites containing combinations of 25 and 75 kDa microspheres in equal amounts released over 90-95 days. Pharmacodynamic studies showed that composites containing only 25 kDa microspheres provided protection against the inflammatory response for 1 month, however, a delayed tissue reaction developed after exhaustion of dexamethasone. This demonstrated that sustained release of the anti-inflammatory agent is required over the entire implant lifetime to control inflammation and prevent fibrosis. Composites fabricated using combinations of 25 kDa and 75 kDa microspheres controlled the tissue reaction for 90 days. This strategy of combining different microsphere populations in the same composite coating can be used to tune the release profiles for the desired extent and duration of release. Such composites offer an innovative solution to control the foreign body response at the tissue-device interface. (C) 2009 Elsevier B.V. All rights reserved.