Using the intravesical delivery route to target the kidney.

Area of Science:

• Nephrology
• Pharmacology
• Drug Delivery Systems

Background:

• Current non-invasive kidney drug delivery methods are limited, creating a need for improved strategies.
• Minimizing systemic side effects while maximizing kidney drug concentration is crucial for effective renal therapies.

Purpose of the Study:

• To evaluate intravesical drug delivery as a non-invasive kidney-targeting strategy in a mouse model.
• To assess the feasibility and effectiveness of delivering therapeutic agents to the kidney via the bladder.

Main Methods:

• Intravesical infusion of molecules up to 500 kDa into mouse bladders.
• Administration of empagliflozin (SGLT2 antagonist) and a chemotherapeutic agent via intravesical route.
• Comparison of intravesical delivery with systemic administration in an orthotopic renal carcinoma model.

Main Results:

• Intravesical infusion successfully delivered molecules to both renal medulla and cortex.
• Empagliflozin effectively targeted proximal tubules, promoting glucose excretion.
• Intravesical chemotherapy demonstrated superior tumor suppression with reduced systemic toxicity compared to intravenous delivery.

Conclusions:

• Intravesical delivery is a feasible and effective strategy for non-invasive kidney targeting.
• This approach enhances renal drug concentration and minimizes systemic exposure, improving therapeutic outcomes.
• Intravesical delivery represents a promising avenue for kidney-targeted therapies and translational research.