Combining Metformin and Drug-Loaded Kidney-Targeting Micelles for Polycystic Kidney Disease.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that leads to eventual renal failure. Metformin (MET), an AMP-activated protein kinase (AMPK) activator already approved for type 2 diabetes, is currently investigated for ADPKD treatment. However, despite high tolerability, MET showed varying therapeutic efficacy in preclinical ADPKD studies.

Improving kidney targeting: The influence of nanoparticle physicochemical properties on kidney interactions.

Kidney-targeted nanoparticles have become of recent interest due to their potential to deliver drugs directly to diseased tissue, decrease off-target adverse effects, and increase overall tolerability to patients with chronic kidney disease that require lifelong drug exposure. Given the physicochemical properties of nanoparticles can drastically affect their ability to extravasate past cellular and biological barriers and access the kidneys, we surveyed the literature from the past decade and analyzed how nanoparticle size, charge, shape, and material density affects passage and interaction with the kidneys. Specifically, we found that nanoparticle size impacted the mechanism of nanoparticle entry into the kidneys such as glomerular filtration or tubular secretion.

The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles.

Chronic kidney disease (CKD) affects 15% of the US adult population. However, most clinically available drugs for CKD show low bioavailability to the kidneys and non-specific uptake by other organs which results in adverse side effects. Hence, a targeted, drug delivery strategy to enhance kidney drug delivery is highly desired.