27 Aug Harvard Bioengineers Develop Synthetic Intestinal Lining to Deliver Drugs, Aid Digestion

MedicalResearch.com Interview with:

Dr. Traverso

Giovanni Traverso, MB, BChir, PhD
Gastroenterologist and biomedical engineer
Division of Gastroenterology at BWH
Instructor of medicine at Harvard Medical School

MedicalResearch.com: What is the background for this study?

Response: We began working on this project with the goal to develop liquid drug formulations that could offer an easier-to-swallow alternative to capsules, especially for children. We started to think about whether we could develop liquid formulations that could form a synthetic epithelial lining that could then be used for drug delivery, making it easier for the patient to receive the medication by providing drugs in extended release formats.

We discovered that an enzyme called catalase could help assemble molecules of dopamine into the polymer (poly-dopamine). These polymers have muco-adhesion properties, which means that after polymerization, the polymer can attach to the tissue very strongly. Also, catalase is found throughout the digestive tract, with especially high levels in the upper region of the small intestine. This is the first example, to the best of our knowledge, of small intestinal targeting system enabled through in-situ tissue-enzyme-catalyzed polymerization.

The coating lasts up to 24 hours, after which it is shed and excreted based on experiments we conducted in pigs.

MedicalResearch.com: What are the main findings? 

Response: By making use of enzymes found in the digestive tract, we have devised a way to apply a temporary synthetic coating to the lining of the small intestine. This coating can be adapted to deliver drugs, aid in digestion, or prevent nutrients such as glucose from being absorbed.

Specifically, we identified a specific enzyme called catalase, that can turn individual monomer/building blocks into polymeric films. We focused on the adhesive system that mussels use for sticking to rocks, and developed a system that could be ingested as a liquid with building blocks (dopamine) and have it form a coating film (poly-dopamine) in the small intestine. We call these Gastrointestinal Synthetic Epithelial Linings or GSEL.

In a study conducted in pigs, we demonstrated that we could use this approach to simplify the delivery of medications that normally have to be taken multiple times per day. We also modified the coatings to deliver the enzyme lactase, which helps people digest the milk sugar lactose. We could also form a barrier in the small intestine to block glucose absorption, which could offer a new strategy to treat diabetes or obesity.

MedicalResearch.com: Might this system be used to treat pernicious anemia?

Response: Perhaps though we haven’t investigated the delivery of vitamin B12.

MedicalResearch.com: What should readers take away from your report?

 Response: By making use of enzymes found in the digestive tract, we have devised a way to apply a temporary synthetic coating to the lining of the small intestine. This coating can be adapted to deliver drugs, aid in digestion, or prevent nutrients such as glucose from being absorbed. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We evaluated the GSEL system on tissue samples from human subjects.  We were reassured by the strong adhesion observed in the human small intestinal samples.  Given the significant set of applications we are actively pursuing further safety studies and determining the optimal applications to develop initially for GSEL.  We anticipate first in human studies in the next 3-5 years.

This work was supported by the Bill and Melinda Gates Foundation grants (OPP1179091), the NIH (EB000244) and funds from the Department of Mechanical Engineering, MIT. Traverso and co-authors declare submission of provisional patent applications describing the materials and applications of GSELs described here. Complete details of all relationships for profit and not for profit for Traverso can be found at the following link: www.dropbox.com/sh/szi7vnr4a2ajb56/AABs5N5i0q9AfT1IqIJAE-T5a?dl=0 

Citation:

Gastrointestinal synthetic epithelial linings 

BY JUNWEI LI, THOMAS WANG, AMEYA R. KIRTANE, YUNHUA SHI, ALEXIS JONES, ZAINA MOUSSA, AARON LOPES, JOY COLLINS, SIDDARTHA M. TAMANG, KAITLYN HESS, RAMEEN SHAKUR, PARAMESH KARANDIKAR, JUNG SEUNG LEE, HEN-WEI HUANG, ALISON HAYWARD, GIOVANNI TRAVERSO

SCIENCE TRANSLATIONAL MEDICINE26 AUG 2020

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Last Updated on August 27, 2020 by Marie Benz MD FAAD