Chitosan-based nanoparticles for topical genetic immunization
Chitosan-based nanoparticles for topical genetic immunization
复制标题
DOI：
10.1016/s0168-3659(01)00407-2
复制
发表时间：
2001-08-10
影响因子：
10.8
通讯作者：
Mumper, RJ
中科院分区：
文献类型：
--
作者：
Cui, ZR;Mumper, RJ
许多研究报道了基因疫苗在动物模型中预防和治疗多种传染病的用途。最近使用基因枪进行的人体临床研究验证了直接靶向皮肤活表皮中的树突状细胞（朗格汉氏细胞）的概念。然而，目前尚不清楚基因枪技术或其他无针设备是否具有商业可行性。我们研究的目的是研究含有质粒 DNA (pDNA) 的基于壳聚糖的纳米粒子作为遗传免疫的潜在方法的局部应用。研究了两种类型的纳米颗粒：(i) pDNA 缩合壳聚糖纳米颗粒，和 (ii) 预制阳离子壳聚糖/羧甲基纤维素 (CMC) 纳米颗粒上包覆有 pDNA。这些研究表明，壳聚糖和壳聚糖低聚物都可以与 CMC 复合，形成稳定的阳离子纳米粒子，用于后续的 pDNA 涂层。选定的 pDNA 包被的纳米粒子（pDNA 高达 400 微克/毫升）对于血清的攻击是稳定的。几种不同的含有 pDNA 的基于壳聚糖的纳米粒子在局部应用 24 小时后，在小鼠皮肤中产生可检测和可量化的荧光素酶表达水平，并在 28 天时产生显着的抗原特异性 IgG Liter 表达 β-半乳糖苷酶。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Numerous studies have reported the prophylactic and therapeutic use of genetic vaccines for combating a variety of infectious diseases in animal models. Recent human clinical studies with the gene gun have validated the concept of direct targeting of dendritic cells (Langerhan's cells) in the viable epidermis of the skin. However, it is unclear whether the gene gun technology or other needle-free devices will become commercially viable. The objective of our studies was to investigate the topical application of chitosan-based nanoparticles containing plasmid DNA (pDNA) as a potential approach to genetic immunization. Two types of nanoparticles were investigated: (i) pDNA-condensed chitosan nanoparticles, and (ii) pDNA-coated on preformed cationic chitosan/carboxymethylcellulose (CMC) nanoparticles. These studies showed that both chitosan and a chitosan oligomer can complex CMC to form stable cationic nanoparticles for subsequent pDNA coating. Selected pDNA-coated nanoparticles (with pDNA up to 400 mug/ml) were stable to challenge with serum. Several different chitosan-based nanoparticles containing pDNA resulted in both detectable and quantifiable levels of luciferase expression in mouse skin 24 h after topical application, and significant antigen-specific IgG Liter to expressed beta -galactosidase at 28 days. (C) 2001 Elsevier Science B.V. All rights reserved.