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利用阳离子PLGA纳米粒涂层式透皮微针可实现甲型H1N1流感DNA疫苗的高效体液免疫
来源于:J Control Release | 作者:纳米医学网 | 发布时间:2017-06-01 | 浏览:9837


      皮内DNA接种可以有效克服传统肌肉疫苗接种的实际缺陷,是一种很有前途的免疫方法。然而,目前尚难有复合物将DNA疫苗直接递送于皮肤中的目标细胞。

     

      韩国Advanced Institute of Science and Technology的学者成功开发了一种皮内H1N1 DNA疫苗递送平台——使用PLGA / PEI(聚乳酸-羟基乙酸/聚乙烯亚胺)纳米粒子(NPS)为涂层的微针(MN)实现了皮内接种的设想。首先,这种不锈钢微针表面富有硅烷涂层以增强微针亲水性,可以充分提高PLGA / PEI聚合物的吸附效率;再将PLGA / PEI聚合物将以干粉形式包覆在微针表面以避免局部聚集。如此处理的涂层可迅速在皮肤模型内溶解(5min内),而且与肌内聚合物递送或直接微针接种裸DNA疫苗的方式相比较,本方法可引起更大的体液免疫反应。另外,研究还进一步优化制备氮磷比,发现当复合物按6:1的比例封装pDNA疫苗时,在哺乳动物细胞中的转染效率最高。这些结果表明,通过微针涂覆阳离子纳米粒来递送基因疫苗,是实现甲型H1N1流感DNA疫苗皮内免疫可行方法之一。








报道刊物:J Control Release. 2017 Apr 20. doi: 10.1016/j.jconrel.2017.04.027.

论文作者:Seok H, Noh JY, Lee DY, Kim SJ, Song CS, Kim YC






Abstract


Intradermal DNA vaccination is a promising method of immunization that overcomes some practical drawbacks of conventional intramuscular vaccinations. However, it is difficult to deliver DNA vaccines to target cells in the skin and polyplexes. This study outlines the development of an intradermal pH1N1 DNA vaccine delivery platform using microneedles (MNs) coated with a polyplex containing poly lactic-co-glycolic acid/polyethyleneimine (PLGA/PEI) nanoparticles (NPs). Stainless steel MNs with enhanced hydrophilicity have been manufactured by silanization, which improves coating efficiency. MNs coated with the polyplex encapsulating pDNA vaccine were prepared by optimizing the N/P ratio, with a 6:1 ratio showing the highest transfection efficiency in mammalian cells. Polyplexes were coated on MNs without severe aggregation of the polyplex in the dry form. The coated polyplex rapidly dissolved in porcine skin (within 5min) and induced a greater humoral immune response than that of intramuscular polyplex delivery or naked pH1N1 DNA vaccine delivery by a dry-coated MN. These results indicate that intradermal delivery of pDNA vaccines within a cationic polyplex coated on MNs has potential in skin immunizations.

 

 

Keywords:Microneedle; PLGA; Polyethyleneimine (PEI); Skin vaccination; pH1N1 DNA vaccine




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