输药微型电机首次用于治疗胃部细菌感染

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输药微型电机首次用于治疗胃部细菌感染

原创 2017-09-20 SIFIC热点团队 SIFIC感染官微

翻译、检索丨刘金淑（濮阳市油田总医院）

审核丨陈志锦（东莞市厚街医院）

加州大学圣地亚哥分校的纳米工程师们证实了首次用输药微车来治疗胃里的细菌感染的可行性。这些输药小车，每部相当于人类头发宽度的一半，在胃中迅速游动，同时能中和胃酸，然后在所需PH值状态下释放其抗生素货品。研究人员在8月16日的《Nature Communications》上发表了他们的研究结果。

研究人员表示，这种使用微电机传送酸敏感药物来治疗胃肠道疾病是一种有前景的治疗胃病新方法。这项研究是由纳米工程学院的教授Joseph Wang和Liangfang Zhang在加州大学圣地亚哥分校工程学院合作开展的。Wang 和 Liangfang Zhang率先对微电机的体内操作进行了研究，该研究代表了首个药物递送微电机用于治疗细菌感染的案例。

胃酸可以对口服药物具有破坏性，如抗生素和蛋白质类药物。用于治疗胃部细菌感染、溃疡和其他疾病的药物通常整合了附加物质，称为质子泵抑制剂，以抑制胃酸的产生。但是，当质子泵抑制剂服用较长时间或高剂量时，会引起副作用，包括头痛、腹泻和疲劳；在更严重的情况下，它们会引起焦虑或抑郁。

微型电机具有内置的机制，可以中和胃酸，并能成功将药物运送到胃里发挥效用，而无需使用质子泵抑制剂。

加州大学圣地亚哥分校研究小组的博士后研究员Berta esteban-fernandez de Avila表示：“这是一种一步到位的治疗方法，利用微型电机将中和胃酸和治疗作用整合到一起。”

每部微型电机均为涂覆有二氧化钛保护层的球形镁芯，接着是一层抗生素——克拉霉素，以及一种称为壳聚糖的带正电聚合物的外层，使电机能粘附在胃壁上。

这种结合也通过由胃自己的酸燃料的微型电机的推进而增强。 镁核心与胃酸反应，产生氢气微泡流，从而推动微车在胃内往复运动。该反应同时能暂时减少胃酸量，增加pH值，促使微型电机释放药物并进行治疗。正常的胃pH值在24小时内恢复。

研究人员在幽门螺杆菌感染的小鼠身上进行了微型电机的测试。每天口服一次装有临床剂量克拉霉素的微型电机，连续5天。随后，研究人员对每只小鼠胃内的细菌计数进行了评估，发现与联合使用质子泵抑制剂相比较，用相同剂量的抗生素时，微型电机的治疗效果要稍好一些。

微型电机主要由可生物降解材料制成，镁芯和聚合物层能被胃酸溶解而不产生有害残留物。

研究人员说，虽然目前的结果很有希望，但这项工作仍处于早期阶段。该团队正在计划未来的研究，以进一步评估微型电机在体内的治疗效果，并将其与其它治疗胃病的标准疗法进行比较。研究人员还计划对微型电机测试不同的药物组合，以治疗胃部或胃肠道不同部位的多种疾病。总的来说，研究人员表示，这项工作打开了使用合成电机作为体内治疗疾病的主动传输平台的大门。

来源新闻编辑室：加州大学圣地亚哥分校

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Drug-Delivering Micromotors Treat TheirFirst Bacterial Infection in the Stomach



Nanoengineers at the University ofCalifornia San Diego have demonstrated for the first time using micromotors totreat a bacterial infection in the stomach. These tiny vehicles, each abouthalf the width of a human hair, swim rapidly throughout the stomach whileneutralizing gastric acid and then release their cargo of antibiotics at thedesired pH. Courtesy of Laboratory for Nanobioelectronics at UC San Diego.

Nanoengineers at the University ofCalifornia San Diego have demonstrated for the first time using micromotors totreat a bacterial infection in the stomach. These tiny vehicles, each abouthalf the width of a human hair, swim rapidly throughout the stomach while neutralizinggastric acid and then release their cargo of antibiotics at the desired pH.Researchers published their findings on Aug. 16 in Nature Communications.

This micromotor-enabled deliveryapproach is a promising new method for treating stomach and gastrointestinaltract diseases with acid-sensitive drugs, researchers said. The effort is acollaboration between the research groups of nanoengineering professors JosephWang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. Wangand Zhang pioneered research on the in vivo operation of micromotors and thisstudy represents the first example of drug-delivering micromotors for treatingbacterial infection.

Gastric acid can be destructive toorally administered drugs such as antibiotics and protein-basedpharmaceuticals. Drugs used to treat bacterial infections, ulcers and otherdiseases in the stomach are normally taken with additional substances, calledproton pump inhibitors, to suppress gastric acid production. But when takenover longer periods or in high doses, proton pump inhibitors can cause adverseside effects including headaches, diarrhea and fatigue. In more serious cases,they can cause anxiety or depression.

The micromotors have a built-inmechanism to neutralize gastric acid and effectively deliver their drugpayloads in the stomach — without the use of proton pump inhibitors.

“It’s a one-step treatment with thesemicromotors, combining acid neutralization with therapeutic action,” said BertaEsteban-Fernández de ávila, a postdoctoral scholar in Wang’s research group atUC San Diego and a co-first author of the paper.

Each micromotor consists of a sphericalmagnesium core coated with a protective layer of titanium dioxide, followed bya layer of the antibiotic clarithromycin, and an outer layer of apositively-charged polymer called chitosan that enables the motors to stick tothe stomach wall.

This binding is also enhanced by thepropulsion of the micromotors, which is fueled by the stomach’s own acid. Themagnesium cores react with gastric acid, generating a stream of hydrogenmicrobubbles that propel the motors around inside the stomach. This reactionalso temporarily reduces the amount of acid in the stomach, increasing the pHlevel enough to allow the micromotors to release the drug and performtreatment. The normal stomach pH is restored within 24 hours.

Researchers tested the micromotors inmice with Helicobacter pylori infections. The micromotors — packed with aclinical dose of the antibiotic clarithromycin — were administered orally oncea day for five consecutive days. Afterwards, researchers evaluated thebacterial count in each mouse stomach and found that treatment with themicromotors was slightly more effective than when the same dose of antibioticwas given in combination with proton pump inhibitors.

The micromotors are mostly made ofbiodegradable materials. The magnesium cores and polymer layers are dissolvedby gastric acid without producing harmful residues.

Researchers say that while the presentresults are promising, this work is still at an early stage. The team isplanning future studies to further evaluate the therapeutic performance of themicromotors in vivo and compare it with other standard therapies againststomach diseases. Researchers also plan to test different drug combinationswith the micromotors to treat multiple diseases in the stomach or in differentsections of the gastrointestinal tract. Overall, the researchers say that thiswork opens the door to the use of synthetic motors as active delivery platformsfor in vivo treatment of diseases.

Reference: Esteban-Fernández de ávila B,et al. Micromotor-Enabled Active Drug Delivery for In Vivo Treatment of StomachInfection. Nature Communications. Aug. 16, 2017.

This work is supported by the DefenseThreat Reduction Agency Joint Science and Technology Office for Chemical andBiological Defense (grant numbers HDTRA1-13-1-0002 and HDTRA1-14-1-0064) and bythe National Institute of Diabetes and Digestive and Kidney Diseases of theNational Institutes of Health (award number R01DK095168).

Source Newsroom: University ofCalifornia San Diego

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审稿：赵静 孙庆芬

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谢谢老师的分享，路过学习了。