Biodegradable Nanoparticles for Delivering Drugs and Silencing Multiple Genes or Gene activation in Diabetic Nephropathy

N. Soni
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引用次数: 3

Abstract

Dialysis is the only mode of available palliative therapeutic modality to patient with end stage of renal disease. Diabetes is one of the foremost common causes of chronic renal disease and affecting large number of diabetic patients. By many theory, hypothesis and study are carried to understand the pathogenesis of Diabetic kidney disease or complication of diabetes i.e. diabetic nephropathy (DN) and based on pathophysiology many drugs and molecules are being developed targeting enzymes, intracellular proteins, micro RNA, Receptor, channel etc. Genes (like NFE2L2, HD1, RPD3 etc.) responsible for synthesis of transcription factor, proteins, enzymes and cytokine factors, intracellular antioxidant factor all play vital role in pathophysiology of DN. Targeting multiple genes, which play important role in pathophysiology of DN with nanoparticle loaded with siRNA or drugs or combination will not only reduce multiple drug and medication burden but also mitigate the disease faster and with reversal of pathological changes with safety, if the challenges are met. It is possible to target multiple genes, which play vital role in fibrosis and extracellular matrix expansion which are key features of DN with biodegradable particle. Each drug by unique mechanism specifically targeting protein, enzymes, receptor, channel etc. mitigates the progress of DN and multiple drugs are needed to inhibit the various mechanism. The approach of silencing the multiple genes or delivering drugs inside the cell organelles with biodegradable nanoparticles is novel, versatile and target specific to inhibit the progress of DN and to reverse the pathological changes efficiently as compared to drugs/molecules, if challenges of nanoparticle formulation are met. Based on the research till date and available resource suggest it is possible to target multiple genes or protein or enzymes or signaling molecules using biodegradable and biocompatible nanoparticles (NP) loaded with siRNA and drugs or combination of drug and siRNA. Key-wordsDiabetic Nephropathy (DN), Proteinuria, Nanoparticles (NP), siRNA, Pathogenesis INTRODUCTION Diabetes is common cause of end stage renal disease and no ideal therapeutic mode is available. Dialysis is common therapeutic in patient with renal failure. DN is most common complication of diabetes mellitus and is characterized by pathologically by proteinuria, fibrosis, podocyte injury, extracellular matrix expansion, thickening of basement membrane and biochemically raised level of uric acid, serum urea and serum creatinine level and radiological finding on USG is small kidney and oxidative stress plays major role in pathogenesis. [1-2] Ideal Nanocarriers : Nanocarriers should be capable of safely and expeditiously transporting siRNA to the target organ or tissue. Access this article online Quick Response Code Website:
可生物降解纳米颗粒递送药物和沉默多基因或基因激活在糖尿病肾病
透析是终末期肾病患者唯一可行的姑息治疗方式。糖尿病是慢性肾脏疾病最常见的病因之一,影响着大量的糖尿病患者。通过许多理论、假设和研究来了解糖尿病肾病或糖尿病并发症即糖尿病肾病(DN)的发病机制,并基于病理生理学开发了许多针对酶、细胞内蛋白、微RNA、受体、通道等的药物和分子。NFE2L2、HD1、RPD3等负责转录因子、蛋白质、酶和细胞因子、细胞内抗氧化因子合成的基因在DN的病理生理中都起着至关重要的作用。如果遇到挑战,利用纳米颗粒负载siRNA或药物或联合靶向在DN病理生理中起重要作用的多个基因,不仅可以减少多种药物和用药负担,而且可以更快地减轻疾病,并安全逆转病理变化。利用可生物降解颗粒靶向多种基因是可能的,这些基因在纤维化和细胞外基质扩张中起着至关重要的作用,这是DN的关键特征。每种药物都有其独特的机制,专门针对蛋白、酶、受体、通道等减缓DN的进展,需要多种药物来抑制各种机制。与药物/分子相比,生物可降解纳米颗粒沉默多个基因或在细胞器内递送药物的方法是一种新颖、通用和靶向的方法,可以有效地抑制DN的进展,并有效地逆转病理变化,如果纳米颗粒配方面临挑战的话。根据迄今为止的研究和现有资源表明,利用可生物降解和生物相容性的纳米颗粒(NP)装载siRNA和药物或药物和siRNA的组合来靶向多个基因或蛋白质或酶或信号分子是可能的。糖尿病肾病(DN),蛋白尿,纳米颗粒(NP), siRNA,发病机制介绍糖尿病是终末期肾脏疾病的常见病因,目前尚无理想的治疗模式。透析是肾衰竭患者常用的治疗方法。DN是糖尿病最常见的并发症,病理表现为蛋白尿、纤维化、足细胞损伤、细胞外基质扩张、基底膜增厚,尿酸、血清尿素、血清肌酐生化升高,USG表现为小肾,氧化应激在发病机制中起主要作用。[1-2]理想的纳米载体:纳米载体应该能够安全、快速地将siRNA运送到目标器官或组织。在线阅读本文快速响应代码网站:
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