A luminal unfolding microneedle injector for oral delivery of macromolecules.,Nature Medicine

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A luminal unfolding microneedle injector for oral delivery of macromolecules.
Nature Medicine ( IF 58.7 ) Pub Date : 2019-10-07 , DOI: 10.1038/s41591-019-0598-9
Alex Abramson _{1,

2} , Ester Caffarel-Salvador _{1,

2,

3} , Vance Soares _{1,

2} , Daniel Minahan _{1,

2} , Ryan Yu Tian _{1,

2} , Xiaoya Lu _{1,

2} , David Dellal _{2,

3} , Yuan Gao _{1,

2} , Soyoung Kim _{1,

2} , Jacob Wainer _{1,

2} , Joy Collins _{1,

2} , Siddartha Tamang _{1,

2} , Alison Hayward _{1,

2,

4} , Tadayuki Yoshitake _{5,

6} , Hsiang-Chieh Lee _{5,

6} , James Fujimoto _{5,

6} , Johannes Fels _{7,

8} , Morten Revsgaard Frederiksen _{7,

8} , Ulrik Rahbek _{7,

8} , Niclas Roxhed _{1,

2,

9} , Robert Langer _{1,

2,

3,

10,

11} , Giovanni Traverso _{1,

2,

10,

12}

Affiliation

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
Global Research Technologies, Global Drug Discovery, Måløv, Denmark.
Device R&D, Novo Nordisk, Måløv, Denmark.
Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications3-5. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort4, show greater chemical stability at high temperatures6, and do not generate biohazardous needle waste7. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract8. We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.

中文翻译：

一种用于大分子口服递送的腔内展开微针注射器。

胰岛素和其他可注射生物药物已经改变了糖尿病患者的治疗方法1,2，但是患者和医疗保健提供者通常更喜欢使用并开出口服效果不佳的药物3-5。与皮下给药的药物相比，口服制剂可减少患者不适4，在高温下显示出更高的化学稳定性6，并且不会产生对生物有害的针头废物7。生物药物的口服剂型是理想的。但是，大分子药物不易通过胃肠道吸收到血液中8。我们开发了一种可吸收胶囊，称为腔内展开微针注射器，可通过使用一组展开臂将可溶解药物的微针快速推进肠道组织，从而实现口服口服生物药物。在离体人类和体内猪研究期间，该设备始终将微针递送至组织，而不会引起完整的厚度穿孔。使用胰岛素作为模型药物，我们显示，当启动时，管腔展开微针注射器在4小时的采样时间内提供了较快的药代动力学吸收曲线，全身吸收率是皮下注射的10％。具有加载多种微针配方的能力，该设备可以用作口服治疗剂量的大分子药物的平台。腔内展开式微针注射器在4小时的采样时间内提供了较快的药代动力学吸收曲线，并且全身吸收率是皮下注射的10％。具有加载多种微针配方的能力，该设备可以用作口服治疗剂量的大分子药物的平台。腔内展开式微针注射器在4小时的采样时间内提供了较快的药代动力学吸收曲线，并且全身吸收率是皮下注射的10％。具有加载多种微针配方的能力，该设备可以用作口服治疗剂量的大分子药物的平台。

更新日期：2019-10-07

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