Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.

The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space easily. Still, it excludes large complexes such as drugs bound to plasma proteins.

The cell membrane is a lipid bilayer that facilitates cellular drug absorption. Depending on the size, drug molecules can pass through the cell membrane by passive diffusion, bulk flow, or active transport.

The blood-brain barrier comprising capillaries in the brain is highly specialized. Unlike other capillaries, these consist of endothelial cells joined by tight junctions that prevent the diffusion of most hydrophilic substances from passing between the endothelial cells. Only lipophilic molecules and molecules transported actively by carrier proteins gain access to the brain.

Similar to the blood-brain barrier, the blood-CSF barrier is also impervious to most substances. Although the capillary lining of the choroid plexus has gaps to allow the free passage of drugs, the choroidal cells are tightly held together by tight junctions, restricting the entry of molecules. In addition, the CSF‒a clear homogeneous fluid surrounding the central nervous system‒dilutes the drug and prevents achieving a high drug concentration.

The blood-placental barrier separates the mother's blood vessels from the fetal blood vessels using multiple layers of trophoblast cells. Compared to the blood-brain or the blood-CSF, it is not an effective barrier. It allows molecules such as barbiturates, gaseous anesthetics, antibiotics, steroids or narcotic analgesics to easily pass through by simple diffusion, exposing the fetus to teratogens. Drug consumption must be restricted during pregnancy.

Lastly, the blood-testis barrier is formed by neighboring Sertoli cells joined together by tight junctions that restrict drugs from diffusing into nearby capillaries and reaching the spermatids.

Tags
Physiological BarriersDrug DiffusionBlood Endothelial BarrierCell MembraneBlood brain BarrierBlood cerebrospinal Fluid BarrierBlood placenta BarrierBlood testis BarrierDrug AbsorptionLipid BilayerPassive DiffusionActive TransportTight JunctionsHydrophilic SubstancesLipophilic MoleculesTeratogens

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