[Structure and function of blood-tissue barriers].
Pharmacologic effects caused by systemic administration of drugs in some organs are prevented by poor transport of the often large or hydrophilic molecules to the parenchyme. The exclusion of macromolecules from the tissue is called blood-tissue barrier. Common examples for barriers are the blood-brain, the blood-placenta-, the blood-retina-, the blood-testis- and the blood- thymus-barrier. The barriers have a well defined anatomic substrate: for the blood-brain-, the inner blood- retina and the blood-thymus-barrier it is the endothelium, for the blood-placenta-, the outer blood-retina-, the blood-testis- and the blood-thymus-barrier these are epithelial cells in the vicinity of the capillary. Epithelia with barrier-function typically have dense intercellular junctions and few pinocytotic vesicles. They express many transporters for the selective transport and for the exchange of molecules. One group of transporters is responsible for the multi-drug resistance. Inflammations and tumors are the most common causes for disturbances of the blood-tissue-barriers. Strategies available for drug delivery to tissues with barriers include the opening of the barrier and the modification of the drug. The opening of the permeability can be achieved by the co-application of the respective drug with mediators as bradykinin or hyperosmolar concentrations of mannitol. Modifications of the drug include lipidization of the molecule, enclosure into liposomes and coupling to substances that are actively taken up by the cells. The pharmaceutical treatment of organs with blood-tissue barriers requires both an efficacious drug and an special application strategy.
Fröhlich
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Anatomisches Institut, Eberhard-Karls-Universität Tübingen, Germany.
D001693:Biological Transport, Active / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D006801:Humans