Interstitial fluid (IF) is pivotal in maintaining balance within tissues and organs, facilitating molecular transport and supporting homeostasis. Various drug delivery systems, such as long-acting depots or implants, rely on IF to distribute drugs locally before they enter the bloodstream. The volume and accessibility of this fluid directly influence how drugs diffuse and the build-up of the osmotic pressure in areas with high drug concentration, ultimately impacting the performance of the delivery systems. Consequently, differences in free fluid availability contribute to discrepancies in drug delivery in vitro versus in vivo. Accurately estimating the volume of IF in vivo would significantly improve the design of in vitro drug release experiments and enhance the outcomes of animal studies. However, accurately measuring free IF and its effect on drug delivery systems in living organisms poses challenges. In response, we developed a reservoir-membrane subcutaneous (SQ) implant similar to a long-acting drug delivery system. The implant measures fluid availability in surrounding tissues by measuring real-time osmotic pressure changes resulting from fluid permeating through a nanoporous membrane, using an integrated pressure transducer and Bluetooth connectivity. By correlating in vitro and in vivo data using a computational model of molecular transport across the membrane, we estimated a 93 % reduction in free fluid availability in the subcutaneous tissue surrounding the implant as compared to our ideal in vitro setting with implant immersed within sink fluids. Applicable to various implantation sites, our study highlights a practical approach to directly assessing free fluid availability in different tissues, enhancing in vitro drug delivery experimental design and evaluating the performance of drug delivery systems in physiological contexts.

中文翻译：

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通过支持遥测的纳米流体植入物在体内直接测量渗透压来量化间质液


间质液 （IF） 在维持组织和器官内的平衡、促进分子运输和支持体内平衡方面发挥着关键作用。各种药物输送系统，例如长效制剂或植入物，都依靠 IF 在药物进入血液之前将其分配到本地。这种液体的体积和可及性直接影响药物的扩散方式和药物浓度高区域的渗透压积聚，最终影响给药系统的性能。因此，游离液体可用性的差异导致体外与体内药物递送的差异。准确估计体内 IF 的体积将显着改进体外药物释放实验的设计并提高动物研究的结果。然而，准确测量游离 IF 及其对生物体中药物递送系统的影响带来了挑战。作为回应，我们开发了一种类似于长效药物输送系统的储库膜皮下 （SQ） 植入物。该植入物使用集成压力传感器和蓝牙连接，通过测量液体渗透纳米多孔膜引起的实时渗透压变化，从而测量周围组织中的液体可用性。通过使用跨膜分子运输的计算模型将体外和体内数据相关联，我们估计，与我们理想的体外设置相比，植入物周围皮下组织中的游离液可用性减少了 93%，植入物浸入下沉液中。 适用于各种植入部位，我们的研究强调了一种直接评估不同组织中游离液体可用性、增强体外药物递送实验设计和评估药物递送系统在生理环境中的性能的实用方法。