Microfabrication of an asymmetric, multi-layered microdevice for controlled release of orally delivered therapeutics
Microfabrication of an asymmetric, multi-layered microdevice for controlled release of orally delivered therapeutics
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DOI：
10.1039/b800604k
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发表时间：
2008-01-01
期刊：
影响因子：
6.1
通讯作者：
Desai, Tejal A.
中科院分区：
文献类型：
--
作者：
Ainslie, Kristy M.;Kraning, Casey M.;Desai, Tejal A.
建立一个口服给药平台来有效地给药化疗药物不仅可以增加患者的依从性，而且还可能减少药物毒性。微制造装置提供了优于传统药物递送技术的优点。在这里，我们描述了一种多层聚合物载药的微制造装置（微装置）的发展，用于治疗剂的口服给药，它提供了多种治疗剂的单向释放。用三种不同的荧光标记的白蛋白进行成像和治疗剂从多层装置的释放。还观察到胰岛素和化疗剂喜树碱的释放在体外180分钟的过程中以受控方式释放。此外，不对称递送显示在装置/细胞界面处浓缩药物，其中与未保护的载药水凝胶相比，10倍以上的药物渗透肠上皮细胞单层。释放的化疗药物的生物活性表现为结直肠腺癌细胞的细胞抑制。载药水凝胶的细胞抑制作用显著高于对照空水凝胶装载微装置。我们的研究结果得出结论，微制造的水凝胶负载的微型装置导致一个可行的口服化疗药物的输送平台。
The creation of an oral drug delivery platform to administer chemotherapeutic agents effectively can not only increase patient compliance, but also potentially diminish drug toxicity. A microfabricated device offers advantages over conventional drug delivery technology. Here we describe the development of a multi-layered polymeric drug-loaded microfabricated device (microdevice) for the oral delivery of therapeutics, which offers unidirectional release of multiple therapeutics. The imaging and release of therapeutics from the multi-layered device was performed with three different fluorescently labeled albumins. The release of insulin and chemotherapeutic camptothecin was also observed to be released in a controlled manner over the course of 180 min in vitro. Furthermore, asymmetric delivery was shown to concentrate drug at the device/cell interface, wherein 10 times more drug permeated an intestinal epithelial cell monolayer, compared to unprotected drug-loaded hydrogels. The bioactivity of the released chemotherapeutic was shown with cytostasis of colorectal adenocarcinoma cells. Cytostasis of drug loaded hydrogels was significantly higher than control empty hydrogel laden microdevices. Our results conclude that microfabrication of a hydrogel laden microdevice leads to a viable oral delivery platform for chemotherapeutics.