Physiological barriers

A drug needs to overcome certain physical, chemical and biological barriers to reach its molecular and cellular sites of action. The epithelial lining of the gastrointestinal tract and other mucous membranes represent a type of barrier; other barriers are also found after drug penetration into the blood and lymphatic vessels. Most drugs circulating in the blood must distribute to local tissues, a process that can be impeded by certain structures such as the blood-brain barrier.

Source: Gastrointestinal system and the functions. Office on Women’s Health USA Department of Health and Human Services, 2021.

Drugs typically leave the intravascular compartment in post capillary venules, where there are larger gaps between the endothelial cells through which the drug can pass. The distribution of a drug occurs mainly by passive diffusion, whose speed is affected by local ionic and cellular conditions. This section describes the main physical, chemical, and biological barriers in the body, as well as the properties of drugs that favor or disfavor your ability to overcome these barriers.


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Bally, Marcel B., Pierrot Harvie, Frances MP Wong, Spencer Kong, Ellen K. Wasan, and Dorothy L. Reimer. “Biological barriers to cellular delivery of lipid-based DNA carriers.” Advanced drug delivery reviews 38, no. 3 (1999): 291-315.

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