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Electromotive Delivery of Mitomycin C into Human Bladder Wall

Departments of Surgery/Urology [S. M. D. S., G. V., F. M.], Internal Medicine/Clinical Biochemistry [R. M.], and Public Health/Cell Biology [S. D.], "Tor Vergata" University of Rome School of Medicine, 00133 Rome, Italy, and "S. Lucia" Istituto di Ricovero e Cura a Carattere Scientifico Rehabilitation Hospital [A. G.], 00179 Rome, Italy

The aim of this investigation was to establish an appropriate tissue pharmacokinetic model to compare concentrations of mitomycin C (MMC) in the human bladder wall after either passive delivery or electromotive administration (EMDA) and to evaluate the effects of EMDA on tissue morphology and MMC structure.

Tissue sections of human bladder were inserted into two chamber cells with urothelium exposed to donor compartments containing MMC (10 mg in 100 ml of 0.24% NaCl solution) and an anode and with serosa exposed to receptor compartments containing 100 ml of 0.9% NaCl solution and a cathode. Fourteen paired experiments ("current 5 mA/no current") were conducted over 15 min; MMC tissue content was assessed by high-pressure liquid chromatography. Tissue viability and morphology and MMC stability were assessed by trypan blue exclusion test, tissue pH, histological analysis, and mass spectrometry analysis.

MMC concentrations were increased, and variability in drug delivery rate was reduced in all tissue in samples exposed to electric current. Tissues were viable and undamaged histologically, and no MMC structural modification was observed.

In conclusion, EMDA enhances administration of MMC into viable bladder wall tissue and reduces the variability in drug delivery rates.

¹ To whom requests for reprints should be addressed, at Cattedra di Urologia, "Tor Vergata" University of Rome, Via della Ricerca Scientifica PP1, 00133 Rome, Italy. Phone: 39 6 72594894; Fax: 39 6 2024434.

Received 7/17/96. Accepted 1/ 2/97.

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				S. M. Di Stasi, A. Giannantoni, R. Massoud, S. Dolci, P. Navarra, G. Vespasiani, and R. L. Stephen Electromotive versus Passive Diffusion of Mitomycin C into Human Bladder Wall: Concentration-Depth Profiles Studies Cancer Res., October 1, 1999; 59(19): 4912 - 4918. [Abstract] [Full Text] [PDF]