Properties of the Urothelium that Establish the Blood–Urine Barrier and Their Implications for Drug Delivery
The primary function of the urinary bladder is to store and periodically release urine. How the urothelium prevents permeation of water, ions, solutes, and noxious agents back into the bloodstream and underlying tissues as well as serving as a sensor and transducer of physiological and nociceptive stimuli is still not completely understood, and thus its unique functional complexity remains to be fully elucidated. This article reviews the permeation routes across urothelium as demonstrated in extensive morphological and electrophysiological studies on in vivo and in vitro urothelia. We consider the molecular and morphological structures of urothelium and how they contribute to the impermeability of the blood–urine barrier. Based on the available data, the extremely low permeability properties of urothelium can be postulated. This remarkable impermeability is necessary for the normal functioning of all mammals, but at the same time represents limitations regarding the uptake of drugs. Therefore, the current progress to overcome this most resilient barrier in our body for drug therapy purposes is also summarized in this review.
KeywordsBlood–urine barrier Drug delivery Paracellular transport Permeability properties Transcellular transport Transepithelial electrical resistance Uroplakins Urothelium
The study was supported by the Slovenian Research Agency (Grant No. P3-0108). The authors thank Professor Dr. Tung-Tien Sun (New York University Medical School) for his generous gift of uroplakin (anti-AUM) antibodies, Dr. Tina Cirman (Blood Transfusion Centre of Slovenia, Ljubljana) for preparing amniotic membranes, and finally various colleagues from the Medical Faculty of the University of Ljubljana for useful discussions.
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