Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination,ACS Nano

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Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination
ACS Nano ( IF 15.8 ) Pub Date : 2018-10-01 00:00:00 , DOI: 10.1021/acsnano.8b05373
Yanpu He _{1,

2} , Celestine Hong _{1,

2} , Jiahe Li _{1,

2} , MayLin T Howard _{1,

2} , Yingzhong Li _{1,

3} , Michelle E Turvey ₄ , Divakara S S M Uppu ₄ , John R Martin _{1,

2} , Ketian Zhang _{1,

5} , Darrell J Irvine _{1,

3,

5,

6} , Paula T Hammond _{1,

2}

Affiliation

The utility of layer-by-layer (LbL) coated microneedle (MN) skin patches for transdermal drug delivery has proven to be a promising approach, with advantages over hypodermal injection due to painless and easy self-administration. However, the long epidermal application time required for drug implantation by existing LbL MN strategies (15–90 min) can lead to potential medication noncompliance. Here, we developed a MN platform to shorten the application time in MN therapies based on a synthetic pH-induced charge-invertible polymer poly(2-(diisopropylamino) ethyl methacrylate-b-methacrylic acid) (PDM), requiring only 1 min skin insertion time to implant LbL films in vivo. Following MN-mediated delivery of 0.5 μg model antigen chicken ovalbumin (OVA) in the skin of mice, this system achieved sustained release over 3 days and led to an elevated immune response as demonstrated by significantly higher humoral immunity compared with OVA administration via conventional routes (subcutaneously and intramuscularly). Moreover, in an ex vivo experiment on human skin, we achieved efficient immune activation through MN-delivered LbL films, demonstrated by a rapid uptake of vaccine adjuvants by the antigen presenting cells. These features, rapid administration and the ability to elicit a robust immune response, can potentially enable a broad application of microneedle-based vaccination technologies.

中文翻译：

用于快速、完整植入逐层微针药膜的合成电荷可逆聚合物，用于增强透皮疫苗接种

多层（LbL）涂层微针（MN）皮肤贴片用于透皮给药已被证明是一种有前途的方法，由于无痛且易于自我给药，因此比皮下注射更具优势。然而，现有的 LbL MN 策略（15-90 分钟）药物植入所需的较长表皮应用时间可能会导致潜在的药物不依从性。在这里，我们开发了一个 MN 平台，以缩短基于合成 pH 诱导电荷可逆聚合物聚（2-（二异丙氨基）甲基丙烯酸乙酯-b-甲基丙烯酸）（PDM）的 MN 疗法的应用时间，仅需要 1 分钟皮肤将 LbL 薄膜植入体内的插入时间。在 MN 介导的小鼠皮肤中递送 0.5 μg 模型抗原鸡卵清蛋白 (OVA) 后，该系统实现了 3 天以上的持续释放，并导致免疫反应升高，与通过常规途径施用 OVA 相比，体液免疫显着提高，证明了这一点（皮下注射和肌肉注射）。此外，在人体皮肤的离体实验中，我们通过 MN 传递的 LbL 薄膜实现了有效的免疫激活，抗原呈递细胞快速摄取疫苗佐剂证明了这一点。这些特征、快速给药和引发强大免疫反应的能力，有可能使基于微针的疫苗接种技术得到广泛应用。

更新日期：2018-10-01

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