Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination.
Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination.
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合成电荷的可转化聚合物，用于快速，完全植入逐层微针药物膜，以增强透皮疫苗。
DOI：
10.1021/acsnano.8b05373
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发表时间：
2018-10-23
期刊：
影响因子：
17.1
通讯作者：
Hammond PT
中科院分区：
文献类型：
--
作者：
He Y;Hong C;Li J;Howard MT;Li Y;Turvey ME;Uppu DSSM;Martin JR;Zhang K;Irvine DJ;Hammond PT
用于经皮给药的逐层（LbL）涂覆的微针（MN）皮肤贴剂的实用性已被证明是一种有前途的方法，由于无痛和易于自我给药而具有优于皮下注射的优点。然而，现有LbL MN策略的药物植入所需的长表皮应用时间（15至90分钟）可能导致潜在的药物不依从性。在这里，我们开发了一种MN平台，以缩短MN治疗的应用时间，该平台基于合成的pH诱导电荷可逆聚合物聚（2-（二异丙基氨基）乙基甲基丙烯酸酯-b-甲基丙烯酸）（PDM），仅需1分钟的皮肤插入时间即可在体内植入LbL膜。在小鼠皮肤中MN介导的0.5 μg模型抗原鸡卵清蛋白（OVA）递送后，该系统在3天内实现了持续释放，并导致了升高的免疫应答，如通过与通过常规途径（皮下和肌内）施用OVA相比显著更高的体液免疫所证明的。此外，在对人皮肤的离体实验中，我们通过MN递送的LbL膜实现了有效的免疫活化，这通过抗原呈递细胞对疫苗佐剂的快速摄取来证明。这些特点-快速管理和引发强大的免疫反应的能力-可以潜在地使基于微针的疫苗接种技术的广泛应用。
The utility of layer-by-layer (LbL) coated microneedle (MN) skin patches for transdermal drug delivery has been proven 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 to 90 minutes) 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-minute 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.
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DOI：
10.1016/j.trsl.2017.08.002
发表时间：
2017-10
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Natarajan G;Perriotte-Olson C;Bhinderwala F;Powers R;Desouza CV;Talmon GA;Yuhang J;Zimmerman MC;Kabanov AV;Saraswathi V
通讯作者：
Saraswathi V
DOI：
10.1016/j.jconrel.2008.07.032
发表时间：
2008-11-12
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Macdonald M;Rodriguez NM;Smith R;Hammond PT
通讯作者：
Hammond PT
影响因子：
10.8
作者：
Jiang, Yuhang;Arounleut, Phonepasong;Manickama, Devika S.
通讯作者：
Manickama, Devika S.
影响因子：
10.8
作者：
Efremenko, Elena N.;Lyagin, Ilya V.;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.
影响因子：
29.4
作者：
DeMuth, Peter C.;Su, Xingfang;Samuel, Raymond E.;Hammond, Paula T.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.