# Nanotechnology, Nanomedicine, and the Kidney
## 5 Nanotechnology for Renal Therapy
### Drug Delivery
#### 5.1.3 Protein/Peptide-Based Carrier  
During glomerular filtration, low molecular weight (LMW) proteins are excreted with the primary urine and reabsorbed by proximal tubular cells. Reabsorption by the proximal tubular cells is a receptor-mediated endocytosis. After endocytosis, proteins are transported to the lysosome and enzymatically degraded into smaller peptides. Studies using macromolecules, such as chitosan [66] and glucosamine [67], or folate [68] as carriers, have shown that these molecule carriers accumulate and release drugs specifically in the kidney.  
Chitosan is a polysaccharide isolated from crustaceans and has been used in several drug delivery approaches because of its great biocompatibility and degradability. It promotes transmembrane transport across epithelial barriers and has a high affinity to the renal proximal tubular cells.  
Prednisolone is a glucocorticoid drug with several applications in renal medicine. It is used to preserve renal function and control the inflammatory response in renal diseases, such as lupus nephritis and glomerulonephritis, and is used to reduce chronic allograft rejection. [PERSON] et al., conjugated an LMW chitosan with prednisolone and tested this compound in rat models for a minimal change disease. They found that the chitosan-prednisolone conjugate predominantly accumulated in the kidney. The conjugate effectively reduced proteinuria in animals with nephritic diseases, and it helped normalize blood urea nitrogen (BUN), albumin, and serum creatinine [69].  
Ischemia-reperfusion (I/R) injury is the leading cause of acute kidney injury and also complicates kidney transplantation. I/R injury damages the proximal tubular cells, resulting in interstitial inflammation and the activation of tissue repair processes. Triptolide (TP) is a compound that, although beneficial in mouse models of polycystic kidney disease, has only limited therapeutic applications due to its high toxicity. A pro-drug in which triptolide is conjugated to glucosamine (TPG) exhibits significantly lower liver toxicity and appears to accumulate in the kidney [70]. Injection of TPG in a rat model of I/R injury showed that TPG accumulated in the kidney and had less toxic side effects. Most importantly, tubular tissue damage was ameliorated, and the proinflammatory cytokines were found to be reduced [67].  
Folate, or vitamin B9, is a naturally occurring molecule that has recently been described to slow the decline of renal function. Sirolimus is a macrolide used as an immunosuppressivement in kidney transplantation. It also blocks mTOR, a central protein kinase that controls cell growth, proliferation, and survival. In a mouse model for polycystic kidney disease, a genetic disorder that leads to ESRD, the injection of a folate-sirolimus conjugate appeared to inhibit the growth of renal cysts and, thus, slowed the progression of the disease. Compared to unconjugated sirolimus injected mice, the folate-sirolimus-treated animals showed no extrarenal effects, suggesting that the folate conjugate limited the sirolimus effect to the kidney [71].