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首页> 外文期刊>ACS Macro Letters >Synthetic Lift-off Polymer beneath Layer-by-Layer Films for Surface-Mediated Drug Delivery
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Synthetic Lift-off Polymer beneath Layer-by-Layer Films for Surface-Mediated Drug Delivery

机译:用于表面介导的药物递送的层面膜下层的合成剥离聚合物

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摘要

A broad range of biomaterials coatings and thin film drug delivery systems require a strategy for the immobilization, retention, and release of coatings from surfaces such as patches, inserts, and microneedles under physiological conditions. Here we report a polymer designed to provide a dynamic surface, one that first functions as a platform for electrostatic thin film assembly and releases the film once in an in vivo environment. Atom transfer radical polymerization (ATRP) was used to synthesize this polymer poly(o-nitrobenzyl-methacrylate-co-hydroxyethyl-methacrylate-co-poly(ethylene-glycol)-methacrylate) (PNHP), embedded beneath multilayered polyelectrolyte films. Such a base layer is designed to photochemically pattern negative charge onto a solid substrate, assist deposition of smooth layer-by-layer (LbL) polyelectrolyte in mildly acidic buffers and rapidly dissolve at physiological pH, thus lifting off the LbL films. To explore potential uses in the biomedical field, a lysozyme (Lys)/poly(acrylic acid) (PAA) multilayer film was developed on PNHP-coated silicon wafers to construct prototype antimicrobial shunts. Film thickness was shown to grow exponentially with increasing deposition cycles, and effective drug loading and in vitro release was confirmed by the dose-dependent inhibition of Escherichia coli (E. coli) growth. The efficacy of this approach is further demonstrated in LbL-coated microscale needle arrays ultimately of interest for vaccine applications. Using PNHP as a photoresist, LbL films were confined to the tips of the microneedles, which circumvented drug waste at the patch base. Subsequent confocal images confirmed rapid LbL film implantation of PNHP at microneedle penetration sites on mouse skin. Furthermore, in human skin biopsies, we achieved efficient immune activation demonstrated by a rapid uptake of vaccine adjuvant from microneedle-delivered PNHP LbL film in up to 37% of antigen-presenting cells (APC), providing an unprecedented LbL microneedle platform for human vaccination.]]>
机译:<![cdata [ src ='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/amlccd/2017/amlccd.2017.6.issue-11/acsmacrolett.7b00584/20171115/图像/中型/ MZ-2017-00584J_0004.gif“>广泛的生物材料涂料和薄膜药物递送系统需要策略进行固定,保留和从物理学下的斑块,插入件和微针的涂层释放涂层状况。在这里,我们报告了一种设计用于提供动态表面的聚合物,首先用作静电薄膜组件的平台,并在体内环境中释放薄膜。原子转移自由基聚合(ATRP)用于合成该聚合物聚( O) - 硝基苄基 - 甲基丙烯酸酯 - - 乙烯乙基 - 甲基丙烯酸酯 - CO-I> - 聚(乙二醇) - 甲基丙烯酸甲酯)(PNHP),嵌入多层聚电解质膜下方。这种基层被设计成将负电荷照射到固体基质上,帮助沉积在轻度酸性缓冲液中的光滑层 - 逐层(LBL)聚电解质,并在生理pH下迅速溶解,从而提升LBL薄膜。为了探索生物医学领域的潜在用途,在PNHP涂覆的硅晶片上显影了一种溶菌酶(Lys)/聚(丙烯酸)(PAA)多层膜以构建原型抗微生物分流。显示膜厚度随着沉积循环的增加而呈指数呈指数增长,并且通过依赖于依赖性抑制大肠杆菌(大肠杆菌)的生长来证实有效的药物负载和体外释放。在LBL涂覆的微观针线阵列中进一步证明了这种方法的功效最终对疫苗应用感兴趣。使用PNHP作为光致抗蚀剂,将LBL薄膜限制在微针的尖端上,这在贴剂底座上绕过的药物废物。随后的共焦图像证实了小鼠皮肤上微针穿透部位的PNHP的快速LBL薄膜植入。此外,在人体皮肤活组织检查中,我们通过从微针递送的PNHP LBL薄膜的疫苗佐剂的快速摄取来实现高效的免疫活化,该PNHP LBL薄膜高达37%的抗原呈递细胞(APC),为人类疫苗接种提供前所未有的LBL微针平台。]]>

著录项

  • 来源
    《ACS Macro Letters》 |2017年第11期|共5页
  • 作者单位

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Infectious Diseases Interdisciplinary Research Group Singapore-MIT Alliance for Research and Technology (SMART) Singapore Singapore;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Infectious Diseases Interdisciplinary Research Group Singapore-MIT Alliance for Research and Technology (SMART) Singapore Singapore;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

    Koch Institute for Integrative Cancer Research Department of Chemical Engineering and Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139 United States;

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  • 正文语种 eng
  • 中图分类 有机化学;
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