PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.
PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.
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DOI：
10.1016/j.jconrel.2018.09.021
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发表时间：
2018-11-10
期刊：
影响因子：
--
通讯作者：
Burgess DJ
中科院分区：
文献类型：
--
作者：
Gu B;Papadimitrakopoulos F;Burgess DJ
嵌入聚乙烯醇（PVA）水凝胶涂层中的地塞米松释放聚（乳酸-乙醇酸）（PLGA）微球已成功用于抑制植入式葡萄糖传感器的异物反应（FBR）。在本研究中，通过共混两种类型的PLGA聚合物（分子量分别为约25 kDa和113 kDa的RG503H和DLG7E）制备负载地塞米松的PLGA微球，以实现对FBR的长期（6个月）抑制。根据体外药物释放曲线优化微球组成。具有DLG7E/RG503H/地塞米松=70/13.3/16.7重量%组合物的微球，当嵌入PVA水凝胶中时，提供了6个月的连续药物释放。通过将上述微球与仅由 DLG7E 聚合物组成的微球结合在类似的 PVA 水凝胶中，实现了更长（超过 7 个月）的体外药物释放。构建热图来描述每日体外药物释放并阐明可能影响药效反应的可能滞后阶段。这些载药植入物涂层在体内（大鼠模型）进行了研究，结果显示可抑制异物反应 6 个月。这些结果表明，对抗慢性炎症的最低有效每日剂量约为。 0.5×0.5×5 mm 硅植入物（虚拟传感器）周围的涂层每毫克 0.1 µg。因此，这些药物洗脱复合涂层可以确保微型植入装置的长期炎症控制。
The application of dexamethasone releasing poly (lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coatings have been successfully used in the suppression of the foreign body response (FBR) to implantable glucose sensors. In the current study, dexamethasone- loaded PLGA microspheres were prepared by blending two types of PLGA polymers (RG503H and DLG7E with MW of ca. 25 kDa and 113 kDa, respectively) to achieve long-term (6 months) inhibition of the FBR. The microsphere composition was optimized according to the in vitro drug release profiles. Microspheres with DLG7E/RG503H/dexamethasone=70/13.3/16.7 weight % composition, when embedded in a PVA hydrogel, provided a continuous drug release for 6 months. By combining the aforementioned microspheres with microspheres composed solely of the DLG7E polymer within a similar PVA hydrogel realized an even longer (greater than 7 months) in vitro drug release. A heat map was constructed to depict the daily in vitro drug released and elucidate possible lag phases that could affect the pharmacodynamic response. These drug-loaded implant coatings were investigated in vivo (rat model) and showed inhibition of the foreign body response for 6 months. These results suggest that the minimum effective daily dose to counter chronic inflammation is ca. 0.1 µg per mg of coating surrounding a 0.5×0.5×5 mm silicon implant (dummy sensor). Accordingly, these drug-eluting composite coatings can ensure long-term inflammation control for miniaturized implantable devices.
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影响因子：
5.8
作者：
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