Wang, X.; Hu, H.; Wang, Q.; Li, L.; Shen, X.

There is an unmet demand for kidney-targeted non-invasive drug-delivery systems to enhance the therapeutic index and at the same time reduce the systemic side effects. In the present study, we performed a proof-of-concept study to evaluate the validity and efficacy of intravesical delivery for kidney targeting in mice. We demonstrated that intravesical infusion was valid for a retrograde delivery of molecules up to 500 kDa to the kidney. A kinetics study revealed that the ascended molecules could stay hours in the kidney. In particular, empagliflozin, an antagonist of sodium-glucose cotransporter 2 (SGLT2), could efficiently act on the uppermost segment of the kidney tubule system, i.e., the proximal tubules, via the intravesical route, and had an action on glucose excretion. In an orthotopic kidney carcinoma model, intravesical delivery of a chemotherapeutic agent was more efficacious in limiting tumor growth, accompanied with much milder adverse effects on extrarenal organs, compared to a systemic delivery when a same dose was administered. This was due to a higher drug concentration in the kidney and a markedly lower level of drug in the blood achieved by intravesical delivery, demonstrating its kidney-targeting specificity. Thus, the intravesical delivery route has a great potential to benefit kidney therapeutics and research.