Aufbau und Funktion von Blut-Gewebe-Schranken

Zusammenfassung

Die Therapie von Erkrankungen ist oftmals problematisch, weil das erkrankte Gewebe von den Pharmaka nicht in ausreichender Konzentration erreicht wird. Das kommt daher, dass zwischen Blut und Gewebe eine morphologisch definierbare Schranke liegt. Am bekanntesten sind Blut-Hirn-, Blut-Hoden-, Blut- Retina-, Blut-Plazenta- und Blut-Thymus-Schranke. Bei der Blut-Hirn-, der inneren Blut-Retina- und der Blut-Thymus-Schranke bildet das Endothel der Blutkapillare die Schranke. Bei der Blut-Hoden-, der äußeren Blut-Retina- und der Blut-Plazenta-Schranke sind außerhalb der Kapillare liegende Epithelien für die Schrankenwirkung verantwortlich. Neben morphologischen Kennzeichen, wie dichten interzellulären Verbindungen und einem Mangel an Endozytosevesikeln, exprimieren schrankenbildende Epithelien typische Transporterproteine, die zum Beispiel Arzneistoffe aus der Zelle transportieren und so die sog. Multi-Drug Resistance bewirken. Neben Entzündungen führen vor allem Tumoren zu einer Schrankenstörung. Es gibt verschiedene experimentelle Ansätze, wie die Schranken umgangen oder durchbrochen werden können. Sie basieren einerseits auf einer Steigerung der Schrankendurchlässigkeit durch die Verabreichung des Wirkstoffes zusammen mit Entzündungsmediatoren (z. B. Bradykinin) oder mit hyperosmolaren Stoffen (z. B. Mannitol), andererseits auf der chemischen Veränderung des Wirkstoffes durch Einschluss in Liposomen oder Kopplung an Substanzen, die Parenchymzellen aktiv aufnehmen. Für die Behandlung von Erkrankungen mit Blut-Gewebe-Schranke ist es nicht ausreichend, ein effektives Medikaments in der Hand zu haben; man muss zusätzlich der besonderen Situation angepasste geeignete Applikationswege wählen.

Summary

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 acchieved 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.

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