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

Malvika Verma(Massachusetts Institute of Technology), Karan Vishwanath(Massachusetts Institute of Technology), Feyisope Eweje(Brigham and Women's Hospital), Niclas Roxhed(Massachusetts Institute of Technology), Tyler M. Grant(Massachusetts Institute of Technology), Macy Castaneda(Massachusetts Institute of Technology), Christoph Steiger(Brigham and Women's Hospital), Hormoz Mazdiyasni(Massachusetts Institute of Technology), Taylor Bensel(Massachusetts Institute of Technology), Daniel Minahan(Massachusetts Institute of Technology), Vance Soares(Massachusetts Institute of Technology), John A. F. Salama(Massachusetts Institute of Technology), Aaron Lopes(Massachusetts Institute of Technology), Kaitlyn Hess(Massachusetts Institute of Technology), Cody Cleveland(Massachusetts Institute of Technology), Daniel J. Fulop(Massachusetts Institute of Technology), Alison Hayward(Massachusetts Institute of Technology), Joy Collins(Massachusetts Institute of Technology), Siddartha Tamang(Massachusetts Institute of Technology), Tiffany Hua(Massachusetts Institute of Technology), Chinonyelum Ikeanyi(Massachusetts Institute of Technology), Gal Zeidman(Massachusetts Institute of Technology), E. M. Mule(Massachusetts Institute of Technology), Sooraj Boominathan(Massachusetts Institute of Technology), Ellena Popova(Massachusetts Institute of Technology), Jonathan B. Miller(Massachusetts Institute of Technology), Andrew M. Bellinger(Harvard University), David Collins(Boston University), Dalia Leibowitz(Massachusetts Institute of Technology), Shelly Batra(Asha Foundation), Sandeep Ahuja(Asha Foundation), Manju Bajiya(Asha Foundation), Sonali Batra(Asha Foundation), Rohit Sarin(LRS Institute of Tuberculosis and Respiratory Diseases), Upasna Agarwal(LRS Institute of Tuberculosis and Respiratory Diseases), Sunil Khaparde(Government of India), Neeraj Gupta(Safdarjang Hospital), Deepak Gupta(All India Institute of Medical Sciences), Anuj K. Bhatnagar(New Delhi Tuberculosis Center), Kamal Kishore Chopra(New Delhi Tuberculosis Center), Nandini Sharma(Maulana Azad Medical College), Ashwani Khanna(Lok Nayak Jai Prakash Narayan Hospital), Jayeeta Chowdhury(Tata Trusts), Robert Stoner(Massachusetts Institute of Technology), Alexander H. Slocum(Massachusetts Institute of Technology), Michael J. Cima(Massachusetts Institute of Technology), Jennifer Furin(Harvard University), Róbert Langer(Massachusetts Institute of Technology), Giovanni Traverso(Brigham and Women's Hospital)
Science Translational Medicine
March 13, 2019
10.1126/scitranslmed.aau6267
Cited by 50Open Access
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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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