Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

November 28, 2016 at 10:27 am

Science Translational Medicine

Andrew M. Bellinger1,2,3,*, Mousa Jafari1,*, Tyler M. Grant1,3,*, Shiyi Zhang1,*,†, Hannah C. Slater4, Edward A. Wenger5, Stacy Mo1, Young-Ah Lucy Lee1, Hormoz Mazdiyasni1, Lawrence Kogan1, Ross Barman1, Cody Cleveland1,6, Lucas Booth1, Taylor Bensel1, Daniel Minahan1, Haley M. Hurowitz1, Tammy Tai1, Johanna Daily7, Boris Nikolic8, Lowell Wood5, Philip A. Eckhoff5, Robert Langer1,9,10,‡ and Giovanni Traverso1,6,11,‡

1Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

3Lyndra Inc., Watertown, MA 02472, USA.

4Department of Infectious Disease Epidemiology, MRC (Medical Research Council) Centre for Outbreak Analysis and Modelling, Imperial College London, London, U.K.

5Institute for Disease Modeling, Bellevue, WA 98005, USA.

6Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

8Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA 98101, USA.

9Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

10 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

11Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Toward malaria eradication

Although we know how to prevent malaria, we have failed to eliminate this damaging disease. To help the millions of individuals still affected around the world, Bellinger et al. have designed an easy-to-administer device that provides long-lasting delivery of an antimalarial drug. A star-shaped, drug-containing material is packaged into a capsule. When swallowed, the capsule dissolves in the stomach, and the star unfolds, assuming a shape that cannot pass further down the intestine. The star delivers a drug toxic to malaria-carrying mosquitoes for weeks but eventually falls apart and passes harmlessly out of the body. Modeling studies show that long-term delivery of this drug may move us closer to the elimination of this problematic disease by improving patient adherence to treatment.

Abstract

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

FULL TEXT

http://stm.sciencemag.org/content/8/365/365ra157.full

Entry filed under: Antiparasitarios, Biología Molecular, Epidemiología, FIEBRE en el POST-VIAJE, Infecciones emergentes, Infecciones parasitarias, Medicina del viajero, Metodos diagnosticos, Sepsis, Update. Tags: .

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