Electromotive drug administration accelerates intravesical tissue uptake of gemcitabine and docetaxel into porcine bladders: an ex vivo proof-of-concept study

BACKGROUND: Intravesical alternatives to bacillus Calmette-Guérin (BCG) are needed to treat patients with non-muscle-invasive bladder cancer (NMIBC) not responding to BCG or high-risk NMIBC. Electromotive drug administration (EMDA) enhances the penetration of mitomycin C into the bladder wall and could be used also with other drugs. We aimed to investigate whether EMDA accelerates intravesical delivery of gemcitabine and docetaxel as compared to passive diffusion (PD). METHODS: We instilled fifteen porcine bladders with gemcitabine and docetaxel using EMDA or PD. Drug concentrations in the mucosa, muscle, and adventitious layers of the bladder were quantified using reversed-phase high-performance liquid chromatography. RESULTS: Docetaxel mean total tissue penetration increased from 2.9% with PD to 6.4% with EMDA after pretreatment with gemcitabine. When no gemcitabine pretreatment was done, docetaxel absorption was statistically significantly higher with EMDA than with PD. Hyaluronic acid did not improve or worsen penetration and no statistically significant difference was observed between the treatment arm with saline (95% confidence intervals of the mean [95% CI] vs PD: 5.92-19.91) and hyaluronic acid/chondroitin sulphate solution (95% CI vs PD: 7.67-23.32). For gemcitabine, no statistically significant difference was observed among treatment arms. Total gemcitabine tissue penetration was similar in both treatment arms, but EMDA shortened the time needed to achieve similar tissue concentrations compared to passive diffusion, reducing the gemcitabine uptake time by 70 minutes and the docetaxel uptake time by 40 minutes. CONCLUSIONS: EMDA accelerates gemcitabine and docetaxel uptake and enhances intravesical delivery of docetaxel.