Quantifying interstitial fluid by direct osmotic pressure measurements in vivo via telemetry-enabled Nanofluidic...

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.