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Sci Transl Med. 2019 Mar 13;11(483). pii: eaau6267. doi: 10.1126/scitranslmed.aau6267.

A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.

Author information

1
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Tata Center for Technology and Design, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm 10044, Sweden.
7
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
9
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
10
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
11
Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
12
Cardiovascular Division, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
13
Management Sciences for Health, Medford, MA 02155, USA.
14
Boston University School of Public Health, Boston, MA 02118, USA.
15
Operation ASHA, New Delhi 110076, India.
16
National Institute of Tuberculosis and Respiratory Diseases, New Delhi 110030, India.
17
Former Deputy Director General and Head of Central TB Division, Government of India, New Delhi 110011, India.
18
Department of Respiratory Medicine, Safdarjung Hospital, New Delhi 110029, India.
19
Division of Pulmonary and Critical Care Medicine, All India Institute of Medical Sciences, New Delhi 110029, India.
20
Rajan Babu Institute for Pulmonary Medicine and Tuberculosis, New Delhi 110009, India.
21
New Delhi Tuberculosis Centre, New Delhi 110002, India.
22
Department of Community Medicine, Maulana Azad Medical College, New Delhi 110002, India.
23
Lok Nayak Hospital Chest Clinic, New Delhi 110002, India.
24
Tata Trusts, Mumbai 400001, India.
25
MIT Energy Initiative, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
26
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
27
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA 02115, USA.
28
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rlanger@mit.edu ctraverso@bwh.harvard.edu cgt20@mit.edu.
29
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
30
Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
31
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rlanger@mit.edu ctraverso@bwh.harvard.edu cgt20@mit.edu.

Abstract

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.

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