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

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

Leveraging Computational Modeling to Understand Infectious Diseases

“…Several long-acting and extended-release drug delivery methods have also been suggested for PrEP [ 83 ]. A novel method of addressing the need for long-term suppressive coverage that reduces an individual’s pill-taking burden is the long-acting, gastric-retentive drug delivery devices that sustainably deliver drugs over days and months [ 84 ]. To that end, Kirtane et al [ 71 •] developed a gastric-retentive device able to deliver ARV for 7 days after ingestion.…”

Chronic respiratory diseases: An introduction and need for novel drug delivery approaches

“…The pulmonary route is now being investigated as a potential route for administering of TB drugs as it is believed that it could target the drugs more effectively to the lungs, the principal portal entry of M. tuberculosis and primary site of TB disease [118] . Recently the use of a gastric resident delivery system has also been explored and found to provide multigram dosing of TB drugs for several weeks in a swine model [119] .…”

In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms

“…However, besides the concepts mentioned above, the first steps towards more innovative solutions have been made. For instance, Verma and colleagues [52] recently developed a several decimeter-long tubular device that can be inserted via the nasogastric route (Figure 5). The device shall remain in the stomach for weeks, thereby constantly releasing different drugs.…”

“…The device shall remain in the stomach for weeks, thereby constantly releasing different drugs. After drug release is completed, it can be retrieved with the help of a magnet [52].…”

“…Schematic of the intragastric placement ( A ) and detailed view ( B ) of the tubular gastroretentive device proposed by Verma et al and reprinted from Reference [52]. …”