Micro-fractional epidermal powder delivery for improved skin vaccination.

Micro-fractional epidermal powder delivery for improved skin vaccination.
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DOI:
10.1016/j.jconrel.2014.08.006
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发表时间:
2014-10-28
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Wu MX
Wu MX
中科院分区:
其他
文献类型:
--
作者:
Chen X;Kositratna G;Zhou C;Manstein D;Wu MX

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在过去的二十年里,皮肤疫苗接种由于其比肌肉注射疫苗接种的效力有所提高而受到越来越多的关注。然而,技术难度和频繁的局部反应阻碍了其在临床的广泛应用。在当前的研究中,开发了微分表皮粉末递送(EPD)以促进皮肤疫苗接种并最大程度地减少局部不良反应。 EPD 基于皮肤的烧蚀点阵激光或微针治疗,在表皮中产生微通道 (MC) 阵列,然后局部应用粉末药物/疫苗涂层的阵列贴片,将药物/疫苗输送到皮肤中。新型 EPD 在 1 小时内将超过 80% 的磺胺罗丹明 b (SRB) 和模型抗原卵清蛋白 (OVA) 递送到小鼠、猪和人类皮肤中。 OVA 的 EPD 诱导的抗 OVA 抗体滴度与皮内 (ID) 注射相当,并且在递送效率和免疫反应方面比胶带剥离更有效。引人注目的是,微分次给药显着减少了 LPS/CpG 佐剂和 BCG 疫苗的局部副作用,从而使皮肤完全恢复。相比之下,腔内注射会引起严重的局部反应,并持续数周。在降低局部反应原性的同时,OVA/LPS/CpG 和 BCG 疫苗的 EPD 产生了与 ID 注射相当的体液免疫反应。与 ID 注射相比,编码 OVA 的痘苗病毒 EPD 诱导显着更高且持久的分泌干扰素 γ 的 CD8+ T 细胞。总之,EPD 代表了一种有前途的无针、无痛皮肤疫苗接种技术,可降低局部反应原性并提高免疫原性。
Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1 hour. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and improved immunogenicity.
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