Wang Yan, Vaddiraju Santhisagar, Qiang Liangliang, Xu Xiaoming, Papadimitrakopoulos Fotios, Burgess Diane J
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
J Diabetes Sci Technol. 2012 Nov 1;6(6):1445-53. doi: 10.1177/193229681200600626.
Hydrogels alone and in combination with microsphere drug delivery systems are being considered as biocompatible coatings for implantable glucose biosensors to prevent/minimize the foreign body response. Previously, our group has demonstrated that continuous release of dexamethasone from poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites can successfully prevent foreign body response at the implantation site. The objective of this study was to investigate the effect of this composite coating on sensor functionality.
The PLGA microsphere/PVA hydrogel coatings were prepared and applied to glucose biosensors. The swelling properties of the composite coatings and their diffusivity to glucose were evaluated as a function of microsphere loading. Sensor linearity, response time, and sensitivity were also evaluated as a function of coating composition.
The PLGA microsphere/PVA hydrogel composite coating did not compromise sensor linearity (sensors were linear up to 30 mM), which is well beyond the physiological glucose range (2 to 22 mM). The sensor response time did increase in the presence of the coating (from 10 to 19 s); however, this response time was still less than the average reported values. Although the sensitivity of the sensors decreased from 73 to 62 nA/mM glucose when the PLGA microsphere loading in the PVA hydrogel changed from 0 to 100 mg/ml, this reduced sensitivity is acceptable for sensor functionality. The changes in sensor response time and sensitivity were due to changes in glucose permeability as a result of the coatings. The embedded PLGA microspheres reduced the fraction of bulk water present in the hydrogel matrix and consequently reduced glucose diffusion.
This study demonstrates that the PLGA microsphere/PVA hydrogel composite coatings allow sufficient glucose diffusion and sensor functionality and therefore may be utilized as a smart coating for implantable glucose biosensors to enhance their in vivo functionality.
水凝胶单独使用或与微球药物递送系统结合使用，正被视为用于可植入葡萄糖生物传感器的生物相容性涂层，以预防/最小化异物反应。此前，我们团队已证明，地塞米松从聚乳酸-乙醇酸共聚物（PLGA）微球/聚乙烯醇（PVA）水凝胶复合材料中的持续释放能够成功预防植入部位的异物反应。本研究的目的是探究这种复合涂层对传感器功能的影响。
制备PLGA微球/PVA水凝胶涂层并应用于葡萄糖生物传感器。评估复合涂层的溶胀特性及其对葡萄糖的扩散率与微球负载量的关系。还评估了传感器线性、响应时间和灵敏度与涂层组成的关系。
PLGA微球/PVA水凝胶复合涂层并未损害传感器线性（传感器在高达30 mM时呈线性），这远超出生理葡萄糖范围（2至22 mM）。在有涂层的情况下，传感器响应时间确实增加了（从10秒增至19秒）；然而，该响应时间仍低于报告的平均值。尽管当PVA水凝胶中PLGA微球负载量从0变为100 mg/ml时，传感器灵敏度从73 nA/mM葡萄糖降至62 nA/mM葡萄糖，但这种降低的灵敏度对于传感器功能而言是可接受的。传感器响应时间和灵敏度的变化是由于涂层导致葡萄糖渗透性改变所致。嵌入的PLGA微球减少了水凝胶基质中存在的大量水的比例，从而降低了葡萄糖扩散。
本研究表明，PLGA微球/PVA水凝胶复合涂层允许足够的葡萄糖扩散和传感器功能，因此可作为可植入葡萄糖生物传感器的智能涂层，以增强其体内功能。
