Recent advances in interstitial fluid dynamics for diagnostic, targeted drug delivery and precision medicine applications.

Abstract

Interstitial fluid (ISF), the extracellular fluid surrounding tissue cells, has emerged as a promising biofluid for biomarker detection and localized physiological monitoring. Although its clinical use remains limited compared with blood or urine, advances in minimally invasive extraction technologies have expanded research interest in its diagnostic and therapeutic potential. ISF shares biochemical similarities with blood but is more accessible through minimally invasive techniques, offers localized biomarker concentrations, and avoids clotting issues. Recent research has demonstrated that ISF contains a rich profile of biomolecules, including proteins, nucleic acids, metabolites, and cytokines, that are valuable for diagnosing and managing a variety of conditions such as infections, metabolic disorders, cancers, and neurological diseases. Advances in microneedle (MN) technology, wearable biosensors, and minimally invasive extraction methods have enabled the efficient sampling and analysis of ISF, bringing its clinical applications closer to reality. Beyond diagnostics, ISF is now being leveraged in therapeutic applications, particularly in precision medicine and drug delivery. Novel delivery strategies such as MNs, convection-enhanced delivery (CED), electroosmotic flow, and fiber-optic theranostics use ISF as both a conduit and a target environment, especially for conditions like solid tumors, where interstitial fluid pressure (IFP) plays a critical role in treatment efficacy. Simulated ISF models are also being developed to facilitate preclinical drug testing and improve translational success. This review emphasizes the mechanistic physiology of ISF from both human and preclinical/animal models, including its pressure regulation, transport dynamics, and simulated/computational modelling, as the foundation for next-generation drug delivery design. While diagnostic and sampling technologies are summarized for context, the review primarily explores how ISF dynamics guide targeted therapy and precision medicine. Overall, ISF offers a dynamic and responsive medium for next-generation medical applications, combining real-time physiological insight with localized therapeutic action. Furthermore, current research and technological advancements, emphasizing the transformative potential of ISF to bridge diagnostics, personalized therapy, as well as drug development and targeted delivery are reviewed herein.