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In vitro and in vivo performance of dexamethasone loaded PLGA microspheres prepared using polymer blends

机译:使用聚合物共混物制备的地塞米松负载PLGA微球的体外和体内性能

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摘要

The foreign body reaction is the major cause of the dysfunction and relatively short lifetime associated with implanted glucose biosensors. An effective strategy to maintain sensor functionality is to apply biocompatible coatings that elute drug to counter the negative tissue reactions. This has been achieved using dexamethasone releasing poly (lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coating. Accordingly, the biosensor lifetime relies on the duration and dose of drug release from the coating. To achieve long-term drug release mixed populations of microspheres have been used. In the current study, microspheres were prepared by blending low (25 KDa) and high (113 KDa) molecular weight PLGA at different mass ratios to overcome problems associated with mixing multiple populations of microspheres. “Real-time” in vitro studies demonstrated dexamethasone release for approximately 5 months. An accelerated method with discriminatory ability was developed to shorten drug release to less than 2 weeks. An in vivo pharmacodynamics study demonstrated efficacy against the foreign body reaction for 4.5 months. Such composite coatings composed of PLGA microspheres prepared using polymer blends could potentially be used to ensure long-term performance of glucose sensors.
机译:异物反应是与植入的葡萄糖生物传感器相关的功能障碍和寿命相对较短的主要原因。维持传感器功能的有效策略是应用可洗脱药物的生物相容性涂层,以抵消组织的不良反应。这是通过使用地塞米松释放嵌入聚乙烯醇(PVA)水凝胶涂层中的聚乳酸-乙醇酸(PLGA)微球来实现的。因此,生物传感器的寿命取决于药物从涂层释放的持续时间和剂量。为了实现长期药物释放,已经使用了微球的混合种群。在当前的研究中,通过以不同的质量比混合低分子量(25 KDa)和高分子量(113 KDa)的PLGA制备微球,以克服与混合多个微球种群相关的问题。 “实时”体外研究表明地塞米松释放约5个月。已开发出具有鉴别能力的加速方法,以将药物释放缩短至不到2周。一项体内药效学研究表明,异物反应可有效治疗4.5个月。这种由使用聚合物共混物制备的PLGA微球组成的复合涂层可以潜在地用于确保葡萄糖传感器的长期性能。

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