Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
College of Veterinary Medicine, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
J Control Release. 2017 Nov 10;265:66-74. doi: 10.1016/j.jconrel.2017.04.027. Epub 2017 Apr 20.
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.
皮内 DNA 疫苗接种是一种很有前途的免疫方法，它克服了传统肌肉内疫苗接种的一些实际缺点。然而，将 DNA 疫苗递送到皮肤中的靶细胞和多聚物是很困难的。本研究概述了使用涂有多聚物（PLGA/PEI）纳米颗粒（NPs）的多聚物的微针（MN）来开发 pH1N1 DNA 疫苗皮内递药平台。通过硅烷化制造了具有增强亲水性的不锈钢 MN，这提高了涂层效率。通过优化 N/P 比制备了包封 pDNA 疫苗的多聚物，其中 6:1 的比例在哺乳动物细胞中显示出最高的转染效率。多聚物在 MN 上的涂层在干燥形式下没有严重的多聚物聚集。涂层多聚物在猪皮中迅速溶解（在 5 分钟内），并引起比肌肉内多聚物传递或裸 pH1N1 DNA 疫苗传递更高的体液免疫反应。这些结果表明，在 MN 上涂有阳离子多聚物的 pDNA 疫苗的皮内传递在皮肤免疫中有潜力。
