Graphene multilayers as gates for multi-week sequential release of proteins from surfaces.

Graphene multilayers as gates for multi-week sequential release of proteins from surfaces.
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DOI:
10.1021/nn202607r
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发表时间:
2012-01-24
期刊:
影响因子:
17.1
通讯作者:
Hammond PT
Hammond PT
中科院分区:
材料科学1区
文献类型:
--
作者:
Hong J;Shah NJ;Drake AC;DeMuth PC;Lee JB;Chen J;Hammond PT

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控制不同治疗药物释放的时间和顺序的能力将在改善患者护理和简化临床治疗方案方面发挥关键作用。从薄膜包衣中控制顺序释放各种小分子和大分子提供了一种简单的方法来提供复杂的体内局部给药。在这里,我们表明可以利用某些纳米材料的结构来控制从数小时到数月的释放方案。氧化石墨烯(GO)是一种二维带电纳米材料,可用于在多层薄膜中形成阻挡层,捕获感兴趣的分子以进行受控释放。采用逐层组装法制备了蛋白质负载的多层膜,该多层膜将可水解降解的阳离子聚(β-氨基酯)(Poly 1)与模型蛋白质抗原卵清蛋白(ova)结合在双层结构中,沿着与用于可降解蛋白质膜的正和负官能化GO封端层。没有GO层的Ova释放在小于1小时内发生,但是可以通过改变多层结构中官能化GO的双层的数量来调节释放30至90天。我们证明了蛋白质可以通过在蛋白质加载层之间并入GO层而在每种物质的释放之间具有多日间隙的顺序释放。单个材料对增殖造血干细胞(HSC)的体外毒性试验表明,在Poly 1和GO片存在下,HSC能够在正常培养的整个10天内存活,细胞毒性作用有限。这种方法提供了一种将治疗剂储存在固态薄膜中的新途径,用于以时间控制和顺序的方式进行后续递送。
The ability to control the timing and order of release of different therapeutic drugs will play a pivotal role in improving patient care and simplifying treatment regimes in the clinic. The controlled sequential release of a broad range of small and macromolecules from thin film coatings offers a simple way to provide complex localized dosing in vivo. Here we show that it is possible to take advantage of the structure of certain nanomaterials to control release regimes from a scale of hours to months. Graphene oxide (GO) is a two-dimensional charged nanomaterial that can be used to create barrier layers in multilayer thin films, trapping molecules of interest for controlled release. Protein-loaded polyelectrolyte multilayer films were fabricated using layer-by-layer assembly incorporating a hydrolytically degradable cationic poly(β-amino ester) (Poly1) with a model protein antigen, ovalbumin (ova) in a bilayer architecture along with positively and negatively functionalized GO capping layers for the degradable protein films. Ova release without the GO layers takes place in less than 1 hour, but can be tuned to release from 30 to 90 days by varying the number of bilayers of functionalized GO in the multilayer architecture. We demonstrate that proteins can be released in sequence with multi-day gaps between the release of each species by incorporating GO layers between protein loaded layers. In vitro toxicity assays of the individual materials on proliferating hematopoietic stem cells (HSCs) indicated limited cytotoxic effects with HSCs able to survive for the full 10 days of normal culture in the presence of Poly1 and the GO sheets. This approach provides a new route for storage of therapeutics in a solid-state thin film for subsequent delivery in a time-controlled and sequential fashion.
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发表时间: 2008-11-12
期刊: Journal of controlled release : official journal of the Controlled Release Society
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作者:
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发表时间: 1994-01-20
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影响因子: 64.8
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