The use of biodegradable polymeric nanoparticles in combination with a low-pressure gene gun for transdermal DNA delivery
The use of biodegradable polymeric nanoparticles in combination with a low-pressure gene gun for transdermal DNA delivery
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DOI：
10.1016/j.biomaterials.2007.10.034
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发表时间：
2008-02-01
期刊：
影响因子：
14
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
--
作者：
Lee, Po-Wei;Peng, Shu-Fen;Sung, Hsing-Wen
金颗粒被用作基因经皮传递的载体，积累后可能产生不良的副作用。本研究采用离子凝胶法制备了由壳聚糖（CS）和聚t -谷氨酸（γ - pga）组成的可生物降解纳米颗粒，用于低压基因枪下经皮DNA递送（CS/ γ - pga /DNA）。未掺入γ - pga的常规CS/DNA作为对照。采用小角x射线散射（SAXS）对纳米颗粒的内部结构进行了表征，并用傅里叶变换红外（FT-IR）光谱对纳米颗粒的成分进行了鉴定。CS/ γ - pga /DNA呈球形，尺寸分布相对均匀。相比之下，CS/DNA的大小分布不均匀，呈甜甜圈、棒状或椒盐卷饼状。两种测试纳米颗粒都能够有效地保留被封装的DNA并保护其免受核酸酶降解。与CS/DNA相比，CS/ γ - pga /DNA提高了其在小鼠皮肤中的渗透深度，并增强了基因的表达。这些观察结果可能归因于CS/y-PGA/DNA的内部结构更紧凑，密度比CS/DNA更大，因此具有更大的穿透皮肤屏障的动量。结果表明，CS/ γ - pga /DNA可替代金颗粒作为DNA载体进行基因透皮传递。(c) 2007 Elsevier Ltd.版权所有。
Gold particles have been used as a carrier for transdermal gene delivery, which may cause adverse side effects when accumulated. In this study, biodegradable nanoparticles, composed of chitosan (CS) and poly-T-glutamic acid (gamma-PGA), were prepared by an ionic-gelation method for transdermal DNA delivery (CS/gamma-PGA/DNA) using a low-pressure gene gun. The conventional CS/DNA without the incorporation of gamma-PGA was used as a control. Small-angle X-ray scattering (SAXS) was used to examine the internal structures of test nanoparticles, while identification of their constituents was conducted by Fourier transformed infrared (FT-IR) spectroscopy. The CS/gamma-PGA/DNA were spherical in shape with a relatively homogeneous size distribution. In contrast, CS/DNA had a heterogeneous size distribution with a donut, rod or pretzel shape. Both test nanoparticles were able to effectively retain the encapsulated DNA and protect it from nuclease degradation. As compared with CS/DNA, CS/gamma-PGA/DNA improved their penetration depth into the mouse skin and enhanced gene expression. These observations may be attributed to the fact that CS/y-PGA/DNA were more compact in their internal structures and had a greater density than their CS/DNA counterparts, thus having a larger momentum to penetrate into the skin barrier. The results revealed that CS/gamma-PGA/DNA may substitute gold particles as a DNA carrier for transdermal gene delivery. (c) 2007 Elsevier Ltd. All rights reserved.