Breaking through the barrier: Modelling and exploiting the physical microenvironment to enhance drug transport and efficacy

Pharmaceutical compounds are the main pillar in the treatment of various illnesses. To administer these drugs in the therapeutic setting, multiple routes of administration have been defined, including ingestion, inhalation, and injection. After administration, drugs need to find their way to the intended target for high effectiveness, and this penetration is greatly dependent on obstacles the drugs encounter along their path. Key hurdles include the physical barriers that are present within the body and knowledge of those is indispensable for progress in the development of drugs with increased therapeutic efficacy. In this review, we examine several important physical barriers, such as the blood-brain barrier, the gutmucosal barrier, and the extracellular matrix barrier, and evaluate their influence on drug transport and efficacy. We explore various in vitro model systems that aid in understanding how parameters within the barrier model affect drug transfer and therapeutic effect. We conclude that physical barriers in the body restrict the quantity of drugs that can pass through, mainly as a consequence of the barrier architecture. In addition, the specific physical properties of the tissue can trigger intracellular changes, altering cell behavior in response to drugs. Though the barriers negatively influence drug distribution, physical stimulation of the surrounding environment may also be exploited as a mechanism to control drug release. This drug delivery approach is explored in this review as a potential alternative to the conventional ways of delivering therapeutics. (c) 2022 The Authors. Published by Elsevier B.V.

Automated summary

Pharmaceutical compounds play a crucial role in the treatment of various illnesses. However, their effectiveness is highly dependent on overcoming the physical barriers in the body. This review focuses on important physical barriers like the blood-brain barrier, gut mucosal barrier, and extracellular matrix barrier, and analyzes their impact on drug transport and efficacy. The study also explores the use of physical stimulation as a strategy for controlled drug release.