Kidney-targeted Nanoparticles
Common kidney diseases include pathological changes in primary and secondary glomeruli, renal tubules, renal mediators, and renal blood vessels. In the clinical treatment of kidney disease, hormone shock treatment is often used, supplemented by triptolide tablets and other drugs for maintenance treatment. The toxic and side effects of large doses of hormones and maintenance drugs severely limit the continuous treatment of kidney disease. When kidney disease develops to a later stage, chronic renal failure will occur, and patients have to rely on expensive hemodialysis or kidney transplantation to prolong life, which will bring a heavy burden on patients’ families and society. It is of great significance to research and develop a kidney-targeted drug delivery system to increase kidney drug concentration and reduce toxic and side effects in the clinical treatment of kidney disease.
Physiological Characteristics of the Kidney
The kidney is one of the important organs of drug metabolism and the only way for drugs and their metabolites, and it is itself the target site of drugs. An important functional unit of the kidney—the renal tubules have functions of absorption, secretion, excretion, and exchange under normal physiological conditions, but they are more complicated under pathological conditions. The kidney may have necrosis or apoptosis due to the kidney tubules damage, or it may produce a large number of inflammatory factors, cytokines or extracellular matrix, promoting local inflammation and fibrous scar formation due to the stimulation and activation of renal tubules. Local renal intrinsic cells, especially proximal tubule epithelial cells, overproduce and activate complements induced by pathological factors, play an important role in renal immune injury. Blocking this effect is of great importance to protect normal kidney function and delay the progression of kidney disease. Therefore, proximal tubule cells become the best target for renal targeted drug delivery, which is significant for the study of renal targeted drug delivery system.
Kidney Targeted Nano Drug Delivery System
To achieve this, scientists are actively exploring in the field of kidney-targeted drug delivery systems. Nanoparticles are favored by researchers because of their unique properties. The following nanoparticles have been used for kidney targeting.
Nanoprodrug
There is a sugar molecule-mediated active transport process in the basement membrane and upper part of renal tubular cells. A kidney-targeting prodrug can be prepared by combining a sugar molecule that can be specifically taken up by the renal tubule with a drug. Prodrugs are regenerated into the parent drug in the renal tubules.
Nanoparticle
Patients with kidney disease often develop hyperphosphatemia, which can stimulate the proliferation of parathyroid cell tissue and increase the secretion of parathyroid hormone (PTH), and cause further deterioration of renal function. Type III sodium-phosphorus cotransporter (NaPi) cotransportation gene transfection experiments found that NaPi-III exists on the membrane of human parathyroid cells and participates in the uptake of phosphorus. The expression of NaPi-III transporter was inhibited by small molecule RNA interference (RNAi). The use of chitosan nanoparticles as an RNA gene vector to mediate the transfection of NaPi-III siRNA into HEK293 cells can significantly enhance the cell transfection efficiency, inhibit the proliferation of parathyroid glands, and thereby improve the treatment of secondary hyperthyroidism (SHPT) in patients with chronic renal failure.
Nanoemulsion
Nanoemulsion has a strong solubilizing capacity for poorly soluble drugs, and it can increase the bioavailability of the drug, delay the plasma clearance rate, make the drug have a long circulation effect, and increase the concentration of the drug in the kidney tissue. The self-emulsifying method was used to prepare the nobiletin-loaded nanoemulsions (NOB-NE). After intravenous injection in mice, the concentration of the drug in the kidney tissue increased significantly compared with that in the control group.
Solid lipid nanoparticles (SLN) are nanoparticles with lipids that are solid at room temperature as a matrix. Resveratrol solid lipid nanoparticles were prepared by a high-pressure homogenization method, with a particle size of 125 nm. After intravenous injection in mice, the concentration in renal tissue increased by 1.82 times compared with resveratrol suspension.
Microspheres
The principle of microsphere kidney targeting is that after intra-arterial injection, particles with a particle size greater than 12 μm are blocked in the capillary bed, and the drug is delivered to the kidney tissue through microcirculation. PLGA microspheres coated with Gd-DTPA were prepared by compound emulsion method. The observation by nuclear magnetic resonance proved that microspheres could significantly enhance the mouse kidney targeting effect.