A Luminal Unfolding Microneedle Injector for Oral Delivery of Macromolecules
This week we profile a recent publication in Nature Medicine from Dr. Ester Caffarel-Salvador (pictured) from the laboratory of Dr. Robert Langer at MIT.
Can you provide a brief overview of your lab’s current research focus?
The Langer lab is a huge lab, so it is difficult to summarize the research focus, as there are many different projects ongoing (the lab has almost 200 people). Research in the Langer lab is at the interface of biotechnology and materials science. A major focus is the study and development of polymers to deliver drugs, particularly genetically engineered proteins, DNA and RNAi, continuously at controlled rates for prolonged periods of time. And Dr. Traverso’s subgroup -where the publication came from- focuses on developing the next generation of drug delivery systems to enable safe and efficient delivery of therapeutics as well developing novel ingestible electronic devices for sensing a broad array of physiologic and pathophysiologic parameters.
What is the significance of the findings in this publication?
We developed an ingestible system capable of applying small micro-needle patches in the small intestine to deliver biologics (like insulin) orally. In this body of work we have made 2 significant advances: (1) a capsule which a) senses the pH of the small intestine and releases the device contained in it. b) the capsule breaks down into small pieces and transits out of the gastrointestinal tract (2) a multi-armed microneedle patch system that unfolds once released from the capsule, applying microneedles loaded with insulin to the intestinal wall and then the system dissolves within a few minutes ensuring passage through the gastrointestinal tract. Putting these two areas together, we developed the luminal unfolding microneedle injector or LUMI and demonstrated our capacity to deliver insulin in the small intestine in pigs.
What are the next steps for this research?
While recombinant human insulin was used as a model drug in the study, active pharmaceutical ingredients with broader therapeutic windows and longer half-lives, such as long acting insulin, may be better suited for LUMI-mediated delivery. Additionally, the LUMI could potentially load numerous biomacromolecules mentioned in the microneedle literature, including: vaccines, monoclonal antibodies, enzymes, hormones, RNA, and other compounds currently lacking oral formulations. Further studies will be needed to test the safety and efficacy of the LUMI device in humans.
If you’d like us to mention your funding sources, please list them.
This work was funded in part by a grant from Novo Nordisk, NIH Grant No. EB-00244. A.A. was supported in part by the NSF GRFP fellowship. G.T. was supported in part by the Division of Gastroenterology, Brigham and Woman’s Hospital and the Department of Mechanical Engineering, MIT. M.K., D.D., D.S. were supported by the MIT Undergraduate Research Opportunities Program (UROP) program. N.R. was supported in part by the Olof Viking Bjork scholarship trust. H.L., T.Y. and J.F. were supported in part by NIH R01-CA075289-21.
Photo Reference: Courtesy of Eric J Norman