Targeting renal fibrosis: Mechanisms and drug delivery systems

Renal fibrosis is the common outcome of many chronic kidney diseases (CKD) independent of the underlying etiology. Despite a host of promising experimental data, currently available strategies only ameliorate or delay the progression of CKD but do not reverse fibrosis. One of the major impediments of translating novel antifibrotic strategies from bench to bedside is due to the intricacies of the drug delivery process. In this review, we briefly describe mechanisms of renal fibrosis and methods of drug transfer into the kidney. Various tools used in gene therapy to administer nucleic acids in vivo are discussed. Furthermore, we review the modes of action of protein- or peptide-based drugs with target-specific antibodies and cytokines incorporated in hydrogels. Additionally, we assess an intriguing new method to deliver drugs specifically to tubular epithelial cells via conjugation with ligands binding to the megalin receptor. Finally, plant-derived compounds with antifibrotic properties are also summarized.