Lyndra Therapeutics released its first clinical results based on a single capsule that delivers a steady, week-long supply of Alzheimer's medication.
In a bid to end daily dosing for health conditions that require long-term medication, Lyndra Therapeutics recently released its first clinical results based on delivering a steady, weeklong supply of medication in one capsule to healthy humans.
This early clinical study focused on a capsule delivering memantine hydrochloride, a drug for Alzheimer’s disease.
Despite the challenges in delivering medicine over days or weeks — keeping unreleased compounds stable in a patient’s body while simultaneously releasing medicine in a controlled way — Lyndra has other drug formulations in the queue, including some that target Schizophrenia and HIV.
“We think that oral, long-acting therapies can offer patients a better option in a number of disease states,” said Andrew Bellinger, Lyndra’s chief scientific officer and co-founder.
Less-frequent dosing makes it much more likely that patients stick with treatment regimens, said Gio Traverso, a gastroenterologist and Harvard professor who co-founded Lyndra with Bellinger.
Otherwise, patients can neglect to take medications, and drugs only work when patients take them. “This is sort of a fundamental, enormous problem, you know, whether you're in Boston, San Francisco, or Sub Saharan Africa,” Traverso said.
Lyndra’s technology looks like a pill capsule. As the capsule dissolves in the stomach, it deploys a plastic, asterisk-shaped drug delivery vehicle.
While it remains in the stomach, the asterisk releases drug molecules on a deliberate schedule. At the end of a dosage term, the asterisk disassembles and travels through the GI tract as any other food would.
The capsule is a spin-off of research that began at MIT, Harvard, and Brigham and Women’s Hospital.
So far, Lyndra’s capsule offers longer-term dosing than other capsule-based approaches, like DepoMed’s Swelling Tablet, or IntecPharma’s Accordion Capsule, which deliver drugs for up to a day.
There are other long-acting dosing mechanisms, like implants, injections, and dermal patches that deliver drugs on longer timescales. Traverso and Bellinger prioritized a capsule form factor after concluding that patients prefer pills to shots or patches.
And where some injections or patches can only transfer certain drugs, Lyndra’s device lends itself to drugs with many different chemical attributes, such as hydrophilic and hydrophobic drugs, Bellinger said.
But designing a device for the gastrointestinal tract presented several obstacles.
Before it could address the issue of keeping drugs stable in an acidic environment, the company’s scientists had to design a structure that could emerge from a capsule and stay in the stomach.
In early pig studies, researchers found that making drug delivery vehicles large wasn’t enough to keep them in the stomach. A drug delivery vehicle also had to be rigid enough to survive the routine muscular contractions that sweep food from the stomach to the intestines.
To keep the device in the stomach, the researchers selected a specific polymer — poly (ε-caprolactone) — and tested different geometries for encapsulation and resistance to bending.
Initially, Lyndra’s founders considered a hexagonal shape for their drug delivery vehicle. But the six-armed star design folded better into a capsule while also resisting bending enough to stay in the stomach.
Armed with a structural shell, the research team next had to incorporate functionalities to release drugs according to a specific dosage schedule, and allow the device to exit once that schedule ended.
Their solution was essentially to compartmentalize the asterisk, assigning separate functions to the device’s arms, core, and the links between the two.
The asterisk’s rigid-polymer arms are milled out to accommodate drug matrices based on the decades of work that Dr. Robert Langer — another Lyndra cofounder — did on drug release. “We can formulate the drug suspended in polymer in such a way that we protect it from the acidic gastric environment, and allow it to be active when it’s released,” Bellinger said.
Because each arm is independent, one drug delivery device can deliver six different release formulations, or even six drugs.
The central core of the star doesn’t contain active ingredients. Its flexibility allows the arms to bend into the capsule form.
Yet another distinct polymer joins the arms to the core. By tuning this polymer’s response to an acidic environment, Lyndra’s team can control how quickly the linkers disintegrate in the stomach.
The linkers break down when the device’s work is done, allowing the core and arms to separate and move into the small intestine.
Besides the Alzheimer’s drugs tested in the most recent clinical trial, Lyndra scientists have begun formulations for schizophrenia drugs. Another drug they’re looking into releasing is buprenorphine, a compound used to treat opioid use disorder.
Each drug requires a slightly different formulation for sustained release, but the scientists are hoping to incorporate many different treatments into the basic platform.
First, there’s more testing to be done. It’s not totally clear how dosing will differ from patient to patient, or how different foods may affect the device in the stomach.
And while Lyndra’s most recent results are for week-long dosing, they’re aiming for longer timescales, too. Eventually, Lyndra’s scientists aim to provide capsules that deliver months of medication in a single pill.
Menaka Wilhelm is an independent writer who focuses on technology.
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