- Nanoparticle therapy in AKI
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Chang Seong Kim
2021 ; 2021(1):
- 논문분류 :
- 춘계학술대회 초록집
Nanoparticles were first introduced as colloid-based drug delivery materials in 1978 to enhance the therapeutic efficacy of drugs and reduce toxicity. Nanotechnology refers to the technology of engineering atoms and molecules of submicron units. Nanoparticles improve pharmacokinetics and bio-distribution to enable targeted delivery of drugs, RNA, DNA, and diagnostic substances to specific tissues, cells, and organs. The basic composition of nanoparticles is that there is a nanoparticle core on the innermost side, which can carry drugs or imaging payloads, and there is a membrane surrounding it, and on the outside, a targeting ligand is attached to improve the delivery ability. In particular, various ligands can be attached to the surface of nanoparticles, and not only small molecules, proteins, peptides, and aptamer ligands, but also antibody coatings can be applied to deliver more effective delivery to target organs. The next important feature is that the drug is encapsulated in nanoparticles to lower the Cmax compared to the free drug, thereby reducing toxicity and maintaining the plasma area under the curve similarly. Therefore, using the three main characteristics of nanoparticles: specific delivery to kidney tissue, sustained drug release and steady efficacy, and combining the target ligand minimize the off-target effect that can occur in other organs, it is used for diagnosis and treatment of kidney disease. Various nanoparticles have been used in hypertensive kidney disease, acute kidney injury (AKI), chronic kidney disease, glomerular disease, and kidney cancer. In this lecture, I would like to discuss in more detail the use of nanoparticles mainly in the treatment of AKI. AKI commonly occurs in hospitalized patients (approximately 10–15%), while its prevalence has been reported to exceed 50% in critically ill patients in the intensive care unit. AKI is a complex disease in which a variety of mediators play an important role, including nitric oxide, reactive oxygen species, pro-inflammatory and pro- fibrotic cytokines, among others. Given the paucity of effective therapies for AKI, the use of nanoparticle-based approaches to deliver molecules specifically to the kidney to treat AKI is attractive and it is starting to be explored in animal models. Drug delivery is possible based on various nanoparticles for AKI treatment. The types of nanoparticles are mainly polymeric, inorganic, lipid-based nanoparticles, and hydrogels. In addition, in order to overcome the disadvantage that stem cells or RNA itself have instability when injected into the body, there is an attempt to use it as a therapeutic agent by loading it in nanoparticles. Most of the animal studies were carried out in the ischemic reperfusion injury model, rhabdomyolysis model, and unilateral obstructive nephropathy model. Previous studies showed that nanoparticle-based therapeutics are delivered directly to the macrophage or kidney to improve renal function, anti-inflammatory, anti-apoptotic effect, and anti-fibrotic effect. In the future, nanoparticles are expected to play a game-changer in AKI treatment by minimizing off-target effects while being more bio-compatible.