Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated. The aim of this study was to synthesize and evaluate a thiolated chitosan to improve the efficacy of oral gene delivery systems. Thiolated chitosan was synthesized by introducing thioglycolic acid (TGA) to chitosan via amide bond formation mediated by a carbodiimide. Based on this conjugate, nanoparticles with pDNA were generated at pH 4.0 and 5.0. Cytotoxicity of the thiolated chitosan/pDNA nanoparticles on Caco-2 cells was evaluated. The diameter of thiolated chitosan/pDNA nanoparticles was in the range of 100-200 nm. The zeta potential was determined to be 5-6 mV. Due to stability toward nucleases, the transfection rate of thiolated chitosan/pDNA nanoparticles was fivefold higher than that of unmodified chitosan/pDNA nanoparticles. Lactate dehydrogenase tests for thiolated chitosan/pDNA (pH 4.0 and 5.0) showed that (3.79 +/- 0.23)% and (2.9 +/- 0.13)% cell damage. According to these results, thiolated chitosan represents promising excipients for preparation DNA nanoparticles in nonviral gene delivery system.

译文

:关于安全性方面,正在广泛研究具有人类基因治疗所要求的效率和安全性的非病毒基因递送载体。这项研究的目的是合成和评估巯基壳聚糖,以提高口服基因传递系统的功效。通过经由碳二亚胺介导的酰胺键形成将硫代乙醇酸(TGA)引入壳聚糖中来合成硫醇化的壳聚糖。基于该缀合物,在pH 4.0和5.0下产生具有pDNA的纳米颗粒。评估了巯基化壳聚糖/ pDNA纳米颗粒对Caco-2细胞的细胞毒性。硫醇化壳聚糖/ pDNA纳米颗粒的直径在100-200 nm的范围内。确定ζ电势为5-6mV。由于对核酸酶的稳定性,硫醇化壳聚糖/ pDNA纳米颗粒的转染率是未修饰的壳聚糖/ pDNA纳米颗粒的转染率的五倍。硫醇化壳聚糖/ pDNA(pH 4.0和5.0)的乳酸脱氢酶测试显示,细胞损伤率为(3.79±0.23)%和(2.9±0.13)%。根据这些结果,硫醇化壳聚糖代表了在非病毒基因递送系统中制备DNA纳米粒子的有希望的赋形剂。

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