Nanomedicine in kidney disease

Abstract

Purpose of review: The pathophysiological understanding of kidney-related disorders has profoundly increased; however, tissue-specific and cell-specific treatments in this field remain scarce. Advances in nanomedicine enable alteration of pharmacokinetics and targeted treatments improving efficiency and reducing toxicity. This review addresses recent developments of nanocarriers used for various purposes in the broad field of kidney disease, which may pave a path to new therapeutic and diagnostic solutions employing nanomedicine.

Recent findings: Controlled delivery of antiproliferative medications enables improved treatment of polycystic kidney disease and fibrosis. Directed anti-inflammatory treatment mitigated glomerulonephritis and tubulointerstitial nephritis. Multiple injury pathways in AKI have been targeted, with therapeutic solutions for oxidative stress, mitochondrial dysfunction, local inflammation and improving self-repair mechanisms. In addition to such treatment development, noninvasive early detection methods (minutes after ischemic insult) have been demonstrated as well. Sustained release of therapies that reduce ischemia-reperfusion injury as well as new aspects for immunosuppression bring hope to improving kidney transplant outcomes. The latest breakthroughs in gene therapy are made achievable by engineering the targeted delivery of nucleic acids for new treatments of kidney disease.

Summary: Recent advances in nanotechnology and pathophysiological understanding of kidney diseases show potential for translatable therapeutic and diagnostic interventions in multiple etiologies of kidney disease.

Figure 1.

Advantages of nanoparticles A. Therapeutic molecules are not taken up intracellularly although when loaded in nanoparticles they enter the cell and are released inside. B. Specific cellular targeting with ligands (antibody, peptide etc.) specific to the cell/condition C. Different forms of nanostructures can allow local sustained release of therapeutics. D. Several different molecules are co-delivered to the cell for synergistic effect. E. Nucleic acids (DNA/RNA) are degraded when exposed in the serum although remain protected when loaded in nanoparticles.

Figure 2.

Main types of nanoparticle composition and morphology A. Lipid B. Synthetic and biological polymer C. Inorganic Vesicle shaped nanoparticle (polymersome, liposome) - hydrophilic core can load hydrophilic molecules and hydrophobic bilayer can load hydrophobic molecules. Micelles - Hydrophobic core can load hydrophobic molecules. Inorganic nanoparticles - therapeutic effect of the element itself, and inorganic element core with additional therapeutics

Figure 3.

Particles delivery through the glomerular filtration barrier (GBF): Gold nanoparticles of 3 nM diameter flow freely through the GBF, large vesicle shaped particles of 100 nM diameter do not flow through, Micelles of 20 nM are less stable and some are disrupted to different sized clusters/micelles with drug spilled out to the serum although some of the dye remains in the clusters and continues to flow through the GBF.