New capsule can orally deliver drugs that usually have to be injected

 

  • Coated pill carries microneedles that deliver insulin and other drugs to the lining of the small intestine

 

CAMBRIDGE, MA, USA (October 7, 2019) — Many drugs, especially those made of proteins, cannot be taken orally because they are broken down in the gastrointestinal tract before they can take effect. One example is insulin, which patients with diabetes have to inject daily or even more frequently. In hopes of coming up with an alternative to those injections, MIT engineers, working with scientists from Novo Nordisk, have designed a new drug capsule that can carry insulin or other protein drugs and protect them from the harsh environment of the gastrointestinal tract. When the capsule reaches the small intestine, it breaks down to reveal dissolvable microneedles that attach to the intestinal wall and release drug for uptake into the bloodstream.

„We are really pleased with the latest results of the new oral delivery device our lab members have developed with our collaborators, and we look forward to hopefully seeing it help people with diabetes and others in the future,“ says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute for Integrative Cancer Research.

In tests in pigs, the researchers showed that this capsule could load a comparable amount of insulin to that of an injection, enabling fast uptake into the bloodstream after the microneedles were released.

Langer and Giovanni Traverso, an assistant professor in MIT’s Department of Mechanical Engineering and a gastroenterologist at Brigham and Women’s Hospital, are the senior authors of the study, which appears today in Nature Medicine. The lead authors of the paper are recent MIT PhD recipient Alex Abramson and former MIT postdoc Ester Caffarel-Salvador.

 

Microneedle delivery

Langer and Traverso have previously developed several novel strategies for oral delivery of drugs that usually have to be injected. Those efforts include a pill coated with many tiny needles, as well as star-shaped structures that unfold and can remain in the stomach from days to weeks while releasing drugs.

„A lot of this work is motivated by the recognition that both patients and health care providers prefer the oral route of administration over the injectable one,“ Traverso says.

Earlier this year, they developed a blueberry-sized capsule containing a small needle made of compressed insulin. Upon reaching the stomach, the needle injects the drug into the stomach lining. In the new study, the researchers set out to develop a capsule that could inject its contents into the wall of the small intestine.

Most drugs are absorbed through the small intestine, Traverso says, in part because of its extremely large surface area — 250 square meters, or about the size of a tennis court. Also, Traverso noted that pain receptors are lacking in this part of the body, potentially enabling pain-free micro-injections in the small intestine for delivery of drugs like insulin.

To allow their capsule to reach the small intestine and perform these micro-injections, the researchers coated it with a polymer that can survive the acidic environment of the stomach, which has a pH of 1.5 to 3.5. When the capsule reaches the small intestine, the higher pH (around 6) triggers it to break open, and three folded arms inside the capsule spring open.

Each arm contains patches of 1-millimeter-long microneedles that can carry insulin or other drugs. When the arms unfold open, the force of their release allows the tiny microneedles to just penetrate the topmost layer of the small intestine tissue. After insertion, the needles dissolve and release the drug.

„We performed numerous safety tests on animal and human tissue to ensure that the penetration event allowed for drug delivery without causing a full thickness perforation or any other serious adverse events,“ Abramson says.

To reduce the risk of blockage in the intestine, the researchers designed the arms so that they would break apart after the microneedle patches are applied.

 

Insulin demonstration

In tests in pigs, the researchers showed that the 30-millimeter-long capsules could deliver doses of insulin effectively and generate an immediate blood-glucose-lowering response. They also showed that no blockages formed in the intestine and the arms were excreted safely after applying the microneedle patches.

„We designed the arms such that they maintained sufficient strength to deliver the insulin microneedles to the small intestine wall, while still dissolving within several hours to prevent obstruction of the gastrointestinal tract,“ Caffarel-Salvador says.

Although the researchers used insulin to demonstrate the new system, they believe it could also be used to deliver other protein drugs such as hormones, enzymes, or antibodies, as well as RNA-based drugs.

„We can deliver insulin, but we see applications for many other therapeutics and possibly vaccines,“ Traverso says. „We’re working very closely with our collaborators to identify the next steps and applications where we can have the greatest impact.“

 

Microneedle Drug Delivery

The research was funded by Novo Nordisk and the National Institutes of Health. Other authors of the paper include Vance Soares, Daniel Minahan, Ryan Yu Tian, Xiaoya Lu, David Dellal, Yuan Gao, Soyoung Kim, Jacob Wainer, Joy Collins, Siddartha Tamang, Alison Hayward, Tadayuki Yoshitake, Hsiang-Chieh Lee, James Fujimoto, Johannes Fels, Morten Revsgaard Frederiksen, Ulrik Rahbek, and Niclas Roxhed.

 


Massachusetts Institute of Technology, 07.10.2019 (tB)

Schlagwörter:

MEDICAL NEWS

IU School of Medicine researchers develop blood test for anxiety
COVID-19 pandemic increased rates and severity of depression, whether people…
COVID-19: Bacterial co-infection is a major risk factor for death,…
Regenstrief-led study shows enhanced spiritual care improves well-being of ICU…
Hidden bacteria presents a substantial risk of antimicrobial resistance in…

SCHMERZ PAINCARE

Hydromorphon Aristo® long ist das führende Präferenzpräparat bei Tumorschmerz
Sorgen und Versorgen – Schmerzmedizin konkret: „Sorge als identitätsstiftendes Element…
Problem Schmerzmittelkonsum
Post-Covid und Muskelschmerz
Kopfschmerz bei Übergebrauch von Schmerz- oder Migränemitteln

DIABETES

Wie das Dexom G7 abstrakte Zahlen mit Farben greifbar macht…
Diabetes mellitus: eine der großen Volkskrankheiten im Blickpunkt der Schmerzmedizin
Suliqua®: Einfacher hin zu einer guten glykämischen Kontrolle
Menschen mit Diabetes während der Corona-Pandemie unterversorgt? Studie zeigt auffällige…
Suliqua® zur Therapieoptimierung bei unzureichender BOT

ERNÄHRUNG

Positiver Effekt der grünen Mittelmeerdiät auf die Aorta
Natriumaufnahme und Herz-Kreislaufrisiko
Tierwohl-Fleisch aus Deutschland nur mäßig attraktiv in anderen Ländern
Diät: Gehirn verstärkt Signal an Hungersynapsen
Süßigkeiten verändern unser Gehirn

ONKOLOGIE

Strahlentherapie ist oft ebenso effizient wie die OP: Neues vom…
Zanubrutinib bei chronischer lymphatischer Leukämie: Zusatznutzen für bestimmte Betroffene
Eileiter-Entfernung als Vorbeugung gegen Eierstockkrebs akzeptiert
Antibiotika als Störfaktor bei CAR-T-Zell-Therapie
Bauchspeicheldrüsenkrebs: Spezielle Diät kann Erfolg der Chemotherapie beeinflussen

MULTIPLE SKLEROSE

Multiple Sklerose: Aktuelle Immunmodulatoren im Vergleich
Neuer Biomarker für Verlauf von Multipler Sklerose
Multiple Sklerose: Analysen aus Münster erhärten Verdacht gegen das Epstein-Barr-Virus
Aktuelle Daten zu Novartis Ofatumumab und Siponimod bestätigen Vorteil des…
Multiple Sklerose durch das Epstein-Barr-Virus – kommt die MS-Impfung?

PARKINSON

Meilenstein in der Parkinson-Forschung: Neuer Alpha-Synuclein-Test entdeckt die Nervenerkrankung vor…
Neue Erkenntnisse für die Parkinson-Therapie
Cochrane Review: Bewegung hilft, die Schwere von Bewegungssymptomen bei Parkinson…
Technische Innovationen für eine maßgeschneiderte Parkinson-Diagnostik und Therapie
Biomarker und Gene: neue Chancen und Herausforderungen für die Parkinson-Diagnose…