Malachowski Kate, Breger Joyce, Kwag Hye Rin, Wang Martha O, Fisher John P, Selaru Florin M, Gracias David H
Department of Chemical and Biomolecular Engineering The Johns Hopkins University 3400 N. Charles St., Baltimore, MD 21218 (USA).
Fischell Department of Bioengineering University of Maryland, College Park, MD 20742 (USA).
Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8045-8049. doi: 10.1002/anie.201311047. Epub 2014 Mar 14.
We report on a therapeutic approach using thermo-responsive multi-fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli-responsive poly(N-isopropylacrylamide-co-acrylic acid) hinges. They close above 32 °C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.
我们报告了一种使用热响应式多指药物洗脱装置的治疗方法。这些被称为“theragrippers”的治疗夹采用光刻图案化工艺成型,由刚性聚(富马酸丙酯)段和刺激响应性聚(N-异丙基丙烯酰胺-共-丙烯酸)铰链组成。它们在32°C以上会闭合,使得从低温状态引入体内时能自发地夹住组织。由于治疗夹具有孔隙,theragrippers还可以装载荧光染料和诸如美沙拉嗪及阿霉素等商业药物,这些药物从治疗夹中以一级释放动力学方式洗脱长达七天。在体外模型中,与对照贴片相比,theragrippers增强了阿霉素的递送。我们还将theragrippers放入活猪体内,并可视化了胃中染料的释放情况。这种组织夹持式药物递送装置的设计为药物的持续释放提供了一种有效的策略,可立即应用于胃肠道。