BERKELEY, CA (UroToday.com) - The direct administration of drug solutions into the bladder overcomes systemic adverse effects of drugs used for bladder disease. Recent observations of several receptors for different neurotransmitters at the level of the urothelial cells suggest that the target sites for pharmacologic modulation of bladder dysfunction should be readily available. The vehicle of the drug solution is critical to increasing urothelial permeability. Giannantoni and colleagues from Italy and Pittsburgh have written a review of mechanisms underlying drug transport into the bladder wall that physicians interested in the treatment of painful bladder syndrome would find very interesting.

It is well known that the bladder has a small but finite passive permeability to most substances found in the urine and blood. Modifications of either cellular or tight junction permeability alter the efficacy of the barrier properties of the urothelium. Dimethylsulfoxide is an organic solvent approved for the intravesical treatment of interstitial cystitis. It has anti-inflammatory and bacteriostatic activity. It produces analgesia and nerve blockade, diuresis, cholinesterase inhibition, vasodilatation, and muscle relaxation. It has the unique capability to penetrate living tissues without causing significant damage.

Another compound is chitosan, a polysaccharide composed of glucosamine and N-acetylglucosamine. It is regarded as a biocompatible, biodegradable, and nontoxic polymer. It can induce desquamation of urothelium, thus removing all diffusion barriers. It may be a promising agent in the development of controlled drug delivery systems.

Electromotive drug administration (EMDA) describes the transport of all water-soluble drugs under the influence of an electric field and, unlike passive diffusion, is most effective when using an ionized drug, where the rate of drug transport is proportional to the intensity of the applied current, which largely overrides all other variables.

Liposomes are artificial spherical vesicles consisting of an aqueous core enclosed in one or more phospholipid layers, used as drug carriers and loaded with a great variety of molecules such as small drug molecules, proteins, nucleotides, and even plasmids. The authors note that new physical approaches such as EMDA or in situ delivery systems and bioadhesive liposomes will expand intravesical therapy options in the future. Use of the bladder as a drug delivery system is still in its infancy.

Giannantoni A, Di Stasi SM, Chancellor MB, Costantini E, Porena M, Everaert K

European Urology, 50(6):1183-1193, 2006.

UroToday.com Painful Bladder Syndrome Section

Written by Philip M. Hanno, MD, a Contributing Editor with UroToday.

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