Pills armed with tiny needles could inject insulin other important meds directly

first_imgUnlike traditional pharmaceuticals, which are small molecules that the digestive tract easily absorbs, biologics are typically proteins: large, unwieldy molecules produced by microbes or other living cells. Biologics, which include seven of the 10 top selling drugs by sales in the United States, are more likely to hit a target molecule in the body without side effects because of their large size. But they’re also more liable to degrade in the stomach or be blocked from entering the bloodstream by thick layers of mucus and tightly packed epithelial cells that line the stomach and gut. Getting past these defenses “is honestly one of the biggest challenges and holy grails in drug development,” says Carlo Giovanni Traverso, a gastroenterologist and bioengineer at Harvard Medical School in Boston and the Massachusetts Institute of Technology (MIT) in Cambridge.In recent years, pharmaceutical companies have encapsulated several small proteins, called peptides, in chemicals called permeation enhancers that promote absorption by the small intestine. But most permeation enhancers allow less than 1% of peptides to cross into the bloodstream.Mitragotri’s team at Harvard is trying to improve on the approach. He and his colleagues reported in 2018 in the Proceedings of the National Academy of Sciences that they encapsulated insulin in a liquid that has the consistency of honey. When the capsule dissolves in the small intestine, the viscous liquid gloms onto the lining and briefly disrupts the lipid membrane of the cells on the surface, allowing the insulin or other drugs to be absorbed. Last week, Mitragotri and his colleagues formed a biotech company to commercialize the technology. Similarly, Oramed Pharmaceuticals, a Jerusalem-based biotech company, is testing insulin capsules containing components that shield the protein from digestive acids and enzymes and promote its absorption in the small intestine.Traverso, with Robert Langer, a drug delivery expert at MIT, and their colleagues turned instead to engineering. They developed a hollow pill with one flattened end. The shape, along with the capsule’s center of mass near the flat end, ensures that the pill rights itself in the stomach, with its flat surface facing the stomach lining. Just inside the pill’s flat end, which is made of sugar, sits a tiny tensed spring topped with a needle made from solid insulin. In the moist stomach, the sugar begins to dissolve, eventually allowing the spring to poke the insulin needle into the outer stomach layer, where it dissolves and enters the bloodstream.In rats and pigs, the pill could deliver essentially the same insulin levels into the blood as a subcutaneous injection. And histology studies showed no signs of lasting damage from daily internal needle punctures.”It’s a very smart design,” says Edith Mathiowitz, a biomedical engineer at Brown University. However, she adds, the team needs to ensure that creating even tiny perforations in the stomach doesn’t pose long-term health problems for patients, and that undesirable proteins or bacteria can’t wiggle their way in alongside the insulin.Rani Therapeutics is banking on similar ingenuity. Instead of a spring, Rani’s pills use a chemical reaction set off by the small intestine’s pH to generate carbon dioxide that inflates a tiny balloon. The balloon presses a needle packed with the drug through the intestinal lining. Although it has not published papers on its pills, Rani has completed more than 100 animal studies. In an initial safety study of pills without needles or drugs, people reported no awareness of the device’s balloon as it inflated, Imran says. This year, he adds, the company plans its first clinical trials of pills loaded with octreotide, a biologic that treats acromegaly, a dangerous enlargement of the face, hands, and feet.It could take years for any of these technologies to complete safety and efficacy studies. But because the engineered pills are intended to work with existing drugs, they could spread rapidly if approved, realizing a century-old goal—and the hopes of countless patients. By Robert F. ServiceFeb. 7, 2019 , 2:00 PM Alex Abramson/MIT Pills armed with tiny needles could inject insulin, other important meds directly into the stomach Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe These pills were engineered to drive a tiny needle into the stomach lining.center_img Sign up for our daily newsletter Get more great content like this delivered right to you! Country Email Click to view the privacy policy. Required fields are indicated by an asterisk (*) In 1922, a 14-year-old boy in Toronto, Canada, received the first injection of insulin to treat life-threatening diabetes. The same year, researchers began to test oral insulin formulations, hoping to relieve people with diabetes of daily shots. That effort failed, as have dozens of similar attempts. But realistic hope for oral insulin may finally be here. Researchers report in this issue of Science that they’ve engineered a capsule that, once ingested, pokes a tiny hole in the lining of the stomach to deliver insulin or other so-called biologic medicines that can’t be taken by mouth.Other research groups and companies have also made recent progress in delivering once-injected medicines orally, raising hopes that for many patients, painful injections may become a thing of the past. “This field is really at an exciting stage,” says Samir Mitragotri, a biomedical engineer at Harvard University. “I think it’s going to completely transform how patients take drugs.”Optimism has surged before. But the harsh environment of the stomach and intestine has thwarted many attempts to deliver complex, delicate drugs by mouth. “There are a lot of dead bodies in this space,” says Mir Imran, CEO of Rani Therapeutics, a San Jose, California, company working to commercialize oral biologics. “People keep trying because it’s such an important area.”last_img

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