WCET 2022: Assessing The Safety And Feasibility Of Electromotive Drug Administration In The Ureter In An In-Vivo Animal Model

(UroToday.com) Electromotive Drug Administration or EMDA is a technique used to increase drug delivery to the targeted tissue. It is a device-assisted therapy that amplifies drug transport across biological membranes under the influence of an electric current. The technique uses a low electrical current to induce an amplified movement of a charged drug deeply into the surrounding tissue. In urology, EMDA has been used in the treatment of superficial bladder cancer. It has been shown that EMDA amplifies the drug penetrance and distribution into and through the bladder wall. However, the upper urinary tract is anatomically designed to push liquid down from the kidney to the bladder rapidly. Therefore, delivering and maintaining medications in the upper urinary tract is challenging. To steadily infuse drugs into the ureter and concomitant application EMDA, a ureteral catheter was custom designed with similar equidistant fenestrations on the distal 20 cm corresponding to ureteral length in a medium size pig.


In two pigs, a guidewire was advanced to the renal pelvis. A novel catheter with fenestrations every 5 mm in its distal end was advanced over the guidewire. The guidewire was replaced by an electrical conduction wire. Methylene blue, a water-soluble dye with a net positive charge, was infused through the catheter at 5 ml/min for 20 minutes in both ureters. In the test ureter, using a standard device for EMDA, a pulsed electrical current of 10mA was applied.

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Figure 1: A. Macroscopic blue staining of the EMDA ureter (left side); B & C. The normal architecture of ureter in EMDA and control ureter, respectively, with mild denudation of superficial urothelium; D & E. Dense and sparse staining (arrow) of methylene blue in EMDA ureter and control ureters, respectively.

Macroscopically, dense staining was seen on the urothelium of EMDA ureters (figure 1A). No evidence of ureteral injury was found in either ureter. Both ureters showed mild urothelial cell denudation, probably due to the passage of the EMDA catheter; the deeper tissues revealed no injury (Figure. 1B & C). 

In the EMDA ureters, there was diffuse penetration of methylene blue throughout the urothelium, lamina propria, and muscularis propria. In the control ureter, there was only patchy superficial urothelial staining (Figure. 1D & E). 

This study showed that in the porcine ureter, EMDA increased the penetration of a charged molecule beyond the urothelium up to the muscularis propria.

Presented by: Seyed Hossein Hosseini Sharifi, MD, Department of Urology, University of California, Irvine, Orange, CA, USA

Written by: Seyed Hossein Hosseini Sharifi, MD, Urology Research Associate, Department of Urology, University of California, Irvine, @Sharifi_shh on Twitter during the 39th World Congress of Endo urology and Uro-Technology (WCET), Oct 1 - 4, 2022, San Diego, California. 

References:

  1. Gurpinar, T., Truong, L. D., Wong, H. Y. et al. Electromotive drug administration to the urinary bladder: an animal model and preliminary results. J Urol 156, 1496-1501 (1996).
  2. Hashemi, S., Sahai, A. & Malde, S. Applications of electromotive drug administration in urology. Urol Ann 12, 301-308, doi:10.4103/UA.UA_152_19 (2020).
  3. Di Stasi, S. M. et al. Electromotive versus passive diffusion of mitomycin C into human bladder wall: concentration-depth profiles studies. Cancer Res 59, 4912-4918 (1999).