Postdoctoral associate Junwei Li, lead author of the study, holds an example of a capsule containing their enzyme. Credit: Image by Melanie Gonick/MIT
MIT engineers devise a temporary film that could deliver drugs or aid in digestion and may help treat diabetes, infections, and other conditions.
By making use of enzymes found in the digestive tract, MIT engineers have devised a way to apply a temporary synthetic coating to the lining of the small intestine. This coating could be adapted to deliver drugs, aid in digestion, or prevent nutrients such as glucose from being absorbed.
In a study conducted in pigs, the researchers demonstrated that they could use this approach to simplify the delivery of medications that normally have to be taken multiple times per day. They also modified the coatings to deliver the enzyme lactase, which helps people digest the milk sugar lactose, and to block glucose absorption, which could offer a new strategy to treat diabetes or obesity.
These three applications are fairly distinct, but they offer a sense of the breadth of things that can be done with this approach, says Giovanni Traverso, an MIT assistant professor of mechanical engineering, a gastroenterologist at Brigham and Womens Hospital, and the senior author of the study.
The lining consists of a polymer made from dopamine molecules, which can be consumed as a liquid. Once the solution reaches the small intestine, the molecules are assembled into a polymer, in a reaction catalyzed by an enzyme found in the small intestine.
Junwei Li, a postdoc at MITs Koch Institute for Integrative Cancer Research, is the lead author of the study, which appears inScience Translational Medicine.
The MIT team began working on this project with the goal of trying to develop liquid drug formulations that could offer an easier-to-swallow alternative to capsules, especially for children. Their idea was to create a polymer coating for the intestinal lining, which would form after being swallowed as a solution of monomers (the building blocks of polymers).
Children often arent able to take solid dosage forms like capsules and tablets, Traverso says. 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.
They took their inspiration from nature and began to experiment with a polymer called polydopamine (PDA), which is a component of the sticky substance that mussels secrete to help them cling to rocks. PDA is made from monomers of dopamine the same chemical that acts as a neurotransmitter in the brain.
The researchers discovered that an enzyme called catalase could help assemble molecules of dopamine into the PDA polymer. Catalase is found throughout the digestive tract, with especially high levels in the upper region of the small intestine.
In a study conducted in pigs, the researchers showed that if they deliver dopamine in a liquid solution, along with a tiny amount of hydrogen peroxide (at levels recognized to be safe), catalase in the small intestine breaks the hydrogen peroxide down into water and oxygen. That oxygen helps the dopamine molecules to join together into the PDA polymer. Within a few minutes, a thin film of PDA forms, coating the lining of the small intestine.
These polymers have muco-adhesion properties, which means that after polymerization, the polymer can attach to the intestinal wall very strongly, Li says. In this way, we can generate synthetic, epithelial-like coatings on the original intestinal surface.
Once the researchers developed the coating, they began experimenting with ways to modify it for a variety of applications. They showed that they could attach an enzyme called beta-galactosidase (lactase) to the film, and that this film could then help with lactose digestion. In pigs, this coating improved the efficiency of lactose digestion around 20-fold.
For another application, the researchers incorporated a drug called praziquantel, which is used to treat schistosomiasis, a tropical disease caused by parasitic worms. Usually this drug has to be given three times a day, but using this formulation, it could be given just once a day and gradually released throughout the day. This approach could also be useful for antibiotics that have to be given more than once a day, the researchers say.
Lastly, the researchers showed that they could embed the polymer with tiny crosslinkers that make the coating impenetrable to glucose (and potentially other molecules). This could help in the management of diabetes, obesity, or other metabolic disorders, the researchers say.
In this study, the researchers showed that the coating lasts for about 24 hours, after which it is shed along with the cells that make up the intestinal lining, which is continually replaced. For their studies in pigs, the researchers delivered the solution by endoscopy, but they envision developing a drinkable formulation for human use. The researchers are also developing other alternative formulations, including capsules and pills.
The researchers performed some preliminary safety studies in rats and found that the dopamine solution had no harmful effects. Their studies also suggested that most or all of the dopamine molecules become part of the synthetic coating and do not make it into the tissue or the bloodstream, but the team plans to do additional safety studies to explore any possible effects the dopamine may have.
Moreover, the researchers investigated the nutrient absorption capacity of the intestine after 24 hours and showed no difference between animals that had received the gastrointestinal synthetic epithelial lining (GSEL) and those that hadnt received the GSEL.
Additionally, the team found that the coating was able to stick well to human GI tissue.
Reference: 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 and Giovanni Traverso, 26 August 2020, Science Translational Medicine.DOI: 10.1126/scitranslmed.abc0441
The research was funded by the Bill & Melinda Gates Foundation, the National Institutes of Health, and MITs Department of Mechanical Engineering.
- The kids aren't all right: COVID-19-fueled stress eating, inequities, lack of fitness expected to boost obesity, experts say - USA TODAY - October 18th, 2020
- Hispanics live longer than most Americans, but will the US obesity epidemic change things? - The Conversation US - October 18th, 2020
- Obesity in children on the rise due to remote learning, study shows - WWLTV.com - October 18th, 2020
- How the pandemic is boosting the risk of childhood obesity WHYY - WHYY - October 18th, 2020
- Risk of severe Covid-19 high for obese people, regardless of other factors - Health24 - October 18th, 2020
- The COVID-19 pandemic emphasizes the need to manage patient obesity - Medical Economics - October 18th, 2020
- Learn About the Advice From FIGO on Obesity | Figo - International Federation of Gynecology and Obstetrics - October 18th, 2020
- Bariatric Surgery Associated with 3-Year Increase in Life Expectancy for Obese Patients - Endocrinology Network - October 18th, 2020
- funded study links adolescent brain differences to increased waist circumference - National Institutes of Health - October 18th, 2020
- National Pet Obesity Awareness Day puts spotlight on keeping furry friends at a healthy weight - KING5.com - October 18th, 2020
- Studies Begin to Untangle Obesitys Role in Covid-19 - The New York Times - September 29th, 2020
- Covid-19 has killed more people than obesity in the UK this year - Full Fact - September 29th, 2020
- Relation found between AMI and obesity < Hospital < - KBR - Korea Biomedical Review - September 29th, 2020
- Long-term impact of obesity on patient-reported outcomes and patient satisfaction after lumbar spine surgery: an observational study. - Physician's... - September 29th, 2020
- Recovered Covid patients just cant stop eating - The New Indian Express - September 29th, 2020
- Wellness Expert James Hill Says Healthy Is More Than Weight Loss - Healthline - September 29th, 2020
- Weight Gain Linked to Later Life Incident VTE - MD Magazine - September 29th, 2020
- 18 Percent Of Americans Don't Have Enough To Eat, Which Makes Them...Obese? - Science 2.0 - September 29th, 2020
- Food insecurity in the US increasingly linked to obesity - Medical News Today - September 28th, 2020
- U.S. Adult Obesity Rate Hits Highest Rate Ever Recorded - Club Industry - September 28th, 2020
- Mission: Readiness ties obesity to national security - News - Times Record - September 28th, 2020
- The Intersection Of Obesity, COVID-19, Social Justice And Mental Health - Club Industry - September 28th, 2020
- Experience of Polish Patients with Obesity in Contacts with Medical Pr | PPA - Dove Medical Press - September 28th, 2020
- Cleveland Clinic Study Identifies Weight-Loss Threshold for Cardiovascular and Survival Benefits in Patients with Obesity and Diabetes - Health... - September 28th, 2020
- Coronavirus pandemic could impact cancer rates and care in the future - WKTV - September 28th, 2020
- An obese heart is a silent risk - The Hippocratic Post - September 28th, 2020
- Nonalcoholic Fatty Liver Disease and Heart Failure: Is There a Connection? - Michigan Medicine - September 28th, 2020
- Should India adopt NOVA classification of food? - The Sunday Guardian - September 28th, 2020
- Obesity and the Bitter Pill of Truth - Medscape - September 23rd, 2020
- Obesity and COVID-19: A renewed call to address a growing crisis - World Bank Group - September 23rd, 2020
- Negative pressure wound therapy does not cut infection risk in obese women after cesarean delivery - National Institutes of Health - September 23rd, 2020
- Obesity linked to hospitalisation and ICUs for Covid-19 patients - The Irish Times - September 23rd, 2020
- New Research Shows Potential Utility of Growth Standards to Monitor Healthy Weight in Puppies and May Help Identify Puppies at Risk for Obesity -... - September 23rd, 2020
- SCOTUS, Sallys economic effects and obesity - AL.com - September 23rd, 2020
- Obesity can cause and be consequence of poor sleep - Westside Eagle Observer - September 23rd, 2020
- Health Education Week 2020: Opportunities and Advancements in Obesity Medicine - Medical Economics - September 23rd, 2020
- COVID-19 Recovery Analysis: Assisted Reproductive Technology Market | Increase in Rate of Infertility and Obesity-Related Cases to Boost the Market... - September 23rd, 2020
- Stephanie Yeboah: 'Obesity is a disgusting word... it's just used to scare people' - Telegraph.co.uk - September 23rd, 2020
- Diabetes, Obesity and other five risk factors that can lead to heart failure - India TV News - September 23rd, 2020
- Research finds out a new phenomenon of obesity with the multiple burden of malnutrition in India - Eastern Eye - September 23rd, 2020
- WHO launches guide to boost children's health and well-being in Russian-speaking countries - Russian Federation - ReliefWeb - September 23rd, 2020
- For teens with severe obesity, bariatric surgery works, but is rarely used. Experts say that needs to change - The Detroit News - September 20th, 2020
- Obesity associated with a higher risk for dementia, new study finds - National Institute on Aging - September 20th, 2020
- Your Health First: Top underlying health conditions in North Dakota? Obesity and Type 2 diabetes - KX NEWS - September 20th, 2020
- US adult obesity at highest level ever recorded; Arkansas and Oklahoma rank in top five - 5newsonline.com - September 20th, 2020
- Coronavirus science | Week in review: 'Long Covid', obesity, and will the virus become seasonal? - Health24 - September 20th, 2020
- Mediterranean diet helps offset the health impacts of obesity - Earth.com - September 20th, 2020
- Obese people 70% more at risk of severe COVID-19: Assocham - The Indian Express - September 20th, 2020
- Could interaction between Covid-19 and pre-existing bacteria explain severity in the obese? - Health24 - September 20th, 2020
- Despicable to blame Government for Covid-19 death rate given obesity, says Tory peer - Evening Standard - September 20th, 2020
- If a heavyweight is morbidly obese why is he also fit to box? - Boxing News Online - September 20th, 2020
- Cancer Is on the Rise Among Young People - Discover Magazine - September 20th, 2020
- Letters to the Editor: Sept. 20 - Canon City Daily Record - September 20th, 2020
- Good nutrition can contribute to keeping COVID-19 and other diseases away - Kiowa County Press - September 20th, 2020
- Why COVID-19 is more deadly in people with obesityeven if they're young - Science Magazine - September 8th, 2020
- Higher obesity rates appear to contribute to higher bankruptcy rates in the United States - PsyPost - September 8th, 2020
- Worldwide Non-Invasive Fat Reduction Industry to 2025 - Increasing Prevalence of Obesity Presents Opportunities - ResearchAndMarkets.com - Business... - September 8th, 2020
- New evidence testosterone therapy is effective obesity treatment in men - New Atlas - September 8th, 2020
- Obesity is tied to greater risk of complications from COVID-19 - WWLTV.com - September 8th, 2020
- Pregnancy, Obesity and Nutrition Initiative (PONI): FIGO releases new Supplement - International Federation of Gynecology and Obstetrics - September 7th, 2020
- High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in ARDS with Class III Obesity. - Physician's Weekly - September 7th, 2020
- Global Intragastric Balloon Market (2019 to 2028) - Rise in Government Initiatives Regarding Obesity Presents Opportunities - ResearchAndMarkets.com -... - September 7th, 2020
- Drugs That Fight Diabetes and Obesity May Treat Covid-19 - Bloomberg - September 6th, 2020
- COVID-19 Patients With Obesity Have Higher Viral Load, for Longer - Medscape - September 6th, 2020
- Even half a glass of alcohol increases risk of obesity, study shows - Study Finds - September 6th, 2020
- America's Obesity Epidemic Threatens Effectiveness of Any COVID Vaccine - POZ - September 6th, 2020
- 'Fat-Shaming' Drops in US but UK Public Still Apportion Blame - Medscape - September 6th, 2020
- Calls for tougher regulation to fight obesity - Newsroom - September 6th, 2020
- Consumption of alcohol even in small amounts can result in obesity and metabolic syndrome, suggests study - Firstpost - September 6th, 2020
- World's richest countries grappling with children's reading and math skills, mental well-being and obesity - UNICEF - September 6th, 2020
- Definition of Chronic disease - MedicineNet - August 31st, 2020
- America's Move to Raise A Healthier Generation of Kids ... - August 31st, 2020
- Controlled obesity status: a rarely used concept, but with particular importance in the COVID-19 pandemic and beyond - DocWire News - August 31st, 2020
- Groningen University Hospital to investigate role of obesity in patients with COVID-19 - Innovation Origins - August 31st, 2020
- Obesity and COVID-19: How weight tips the scales to severe COVID-19 illness - The Stanford Daily - August 31st, 2020
- Study finds obese people at higher risk of COVID-19 complications - Times of India - August 31st, 2020
- Childhood obesity could increase the risk of multiple sclerosis in later life - The Conversation UK - August 31st, 2020
- Peter Rhodes on an Indian romance, the risks of obesity and standing up for nice things - expressandstar.com - August 31st, 2020
- Joint Pain Injections Market: Investments by key players is driving the global market - BioSpace - August 31st, 2020
- Why your doctor will not talk to you about obesity - The Standard - August 31st, 2020