PT  - JOURNAL ARTICLE
AU  - Arijit Ghosh
AU  - Wangqu Liu
AU  - Ling Li
AU  - Gayatri Pahapale
AU  - Si Young Choi
AU  - Liyi Xu
AU  - Qi Huang
AU  - Florin M. Selaru
AU  - David H. Gracias
TI  - Autonomous untethered microinjectors for gastrointestinal delivery of insulin
AID  - 10.1101/2022.05.05.490821
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.05.490821
4099  - http://biorxiv.org/content/early/2022/05/05/2022.05.05.490821.short
4100  - http://biorxiv.org/content/early/2022/05/05/2022.05.05.490821.full
AB  - The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging. Macromolecular drugs display low stability and poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that can efficiently penetrate the GI mucosa and deliver insulin systemically. In addition, we performed in vitro studies to characterize insulin release and the penetration capacity of microinjectors and measure in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin trans-mucosally to the systemic circulation at similar levels to intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these novel microinjectors could significantly advance drug delivery across the GI tract mucosa to the systemic circulation.Competing Interest StatementJohns Hopkins University has filed patents related to the technology. Under an option to license agreement between Kley Dom Biomimetics, LLC and the Johns Hopkins University, Prof. D. H. Gracias and the Johns Hopkins University are entitled to royalty distributions related to the technology described in the study discussed in this publication. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. In addition, some of the authors and the Johns Hopkins University have patents/patent applications related to the technology described.