Renal-targeted drug delivery: overcoming barriers and charting the course.

Renal-targeted drug delivery is essential for treating diseases such as acute kidney injury and chronic kidney disease but is hindered by renal physiological barriers. Glomerular filtration and tubular reabsorption greatly limit drug accumulation in renal tissues. Strategies such as prodrugs, small molecule conjugates, macromolecular conjugates, and nanoparticles offer promising solutions to enhance renal specificity and to minimize systemic toxicity. This review summarizes critical challenges and recent advances in renal-targeted drug delivery, examines key factors such as the ligand selection, the effects of size and charge on targeting efficiency, and outlines future directions for the development of kidney disease therapies with greater safety and better efficacy.