Langer study describes once-monthly dosing system for tuberculosis

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The scientific team behind drug delivery company Lyndra Therapeutics described a delivery device capable of releasing large payloads into the stomach over several weeks in a paper published in Science Translational Medicine on Wednesday. While the device is designed to improve compliance for long-term, frequently dosed treatment regimens, such as for tuberculosis, it does require an invasive nasogastric tube for placement and delivery.

In the paper, Robert Langer, Giovanni Traverso and colleagues described the device, dubbed a gastric release system (GRS), as a string of multiple pills along a superelastic nitinol wire with a retainer and tubing at the end. The pills are formulated in a silicon matrix and encapsulated in a polymer coating for sustained delivery.

When the wire is delivered through the nose to the stomach, it forms a cylindrical coil and remains in the stomach until it is retrieved by another nasogastric tube using its magnetic end.

Traverso is a visiting scientist at Massachusetts Institute of Technology, where Langer is a professor.

When an antibiotic-loaded GRS was delivered into pigs via a nasogastric tube and monitored for 28 days before retrieval, it did not damage the GI tract or cause weight loss, and the drug was present in serum for the duration of the study. The group tested two antibiotics commonly used to treat TB: doxycycline hyclate and rifampicin.

While the group used TB drugs as proof of concept due to the long-term, large-dose treatment regimen required, Malvika Verma, a Ph.D. candidate in Langer’s lab and lead author on the paper, told BioCentury it could be applied to help patients finish treatments for many other indications. The group is also developing the system for HCV treatments, “where adherence is also a challenge.”

The group designed the system to accommodate different drugs as it is a “slinky of drug pills,” Verma said. “Each pill can be a different drug or have a different rate of release, so we can incorporate pills in one device to treat many diseases,” such as neuropsychiatric, heart and renal diseases.

The group acknowledged that patient acceptance of a nasogastric tube administration could be a challenge, but its survey of 300 patients from 110 TB treatment centers in India indicated that the delivery route should be feasible.

Verma said the nasogastric tube is necessary because the largest swallowable capsule can only hold 1 mg of drug at most, whereas the tube with this device can deliver drug doses greater than 10 grams.

The MIT group is testing whether the device can be deployed for more than one month, but Verma noted that completing a TB regimen would still require multiple nasogastric tube placements and retrievals. TB treatment regimens last 6-9 months, according to the CDC.

Langer and Traverso are co-founders of Lyndra Therapeutics Inc. (Waterton, Mass.), which is developing oral drug delivery systems for ultra-long drug release. All of the candidates in Lyndra’s pipeline are delivered via a pill, and the company has not licensed the large-dose GRS (see “Star Treatment”).

Last month, Langer and Traverso described an oral delivery device that injects insulin into the stomach to treat diabetes (see “Oral Insulin Innovation”).