Astronauts in space have to exercise for an average of two and a half hours per day to minimise the impacts of muscle atrophy in microgravity. This presents a significant health risk for astronauts undertaking long-haul trips into space, such as US astronaut Mike Kelly who spent 342 days aboard the International Space Station from 2015 to 2016.
The mechanical unloading of the muscles in zero-gravity conditions triggers protein synthesis to decrease and protein degradation to occur, causing the muscles to start wasting. It’s the same reason patients with chronic illnesses that leave them immobile or bedridden also experience muscle atrophy.
Scientists at Houston Methodist Research Institute are now working to combat astronauts’ atrophy in outer space, using a subcutaneously implanted nanofluidic drug delivery system. The device is designed to gradually release very small doses of a drug called formoterol and has now been trialled in mice aboard the International Space Station.
Formoterol is a bronchodilation drug, a type of medication that makes breathing easier by relaxing the muscles in the lungs and widening the airways. It’s a long-acting bronchodilator, meaning it’s used as a maintenance treatment to offset the symptoms of chronic lung diseases like asthma, bronchitis or emphysema.
Alongside these effects, formoterol has been shown to stimulate increased muscle mass at certain doses, which could help our astronauts out. However, these doses also lead to cardiovascular side effects – increased heart rate, decreased blood pressure, reduced plasma potassium concentration – which in the harsh conditions of outer space are far from ideal.
Mitigating side-effects through low-dose drug delivery
The Houston researchers are hoping that the systematic low-dose release of formoterol permitted by the nanofluidic delivery system can prevent muscle wastage while avoiding these cardiac side effects.
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Houston Methodist professor of nanomedicine Dr Alessandro Grattoni says: “It may be possible that adverse effect of formoterol could be mitigated via low-dose sustained delivery. As opposed to bolus administration, which is typically associated with a ‘rollercoaster’ in drug concentration in the body, sustained low dose delivery may prove effective while limiting side effects. However, this needs to be further investigated.”
A group of mice (Mus Musculus) were fitted with the device and sent to space for 56 days, to test the impact sustained delivery of formoterol had on their muscles when they were in zero gravity. Far from merely preventing atrophy, the drug actually stimulated muscle growth in certain areas.
Grattoni says: “Formoterol was effective a preventing muscle atrophy. In fact, we observed an increase in muscle mass, specifically muscles such as the gastrocnemius, soleus and plantaris, that are relevant in standing and numerous movements. In the study subjects flown on the International Space Station, we observed an increase in grip strength of 11%. This is significant, especially in view of the short duration of the study.”
Nanofluidic delivery could help manage multiple medications
This study is the first demonstration that implantable nanofluidic drug delivery systems could be used to maintain astronaut health in outer space. Theoretically, rather than exercising for several hours every day to offset mechanical unloading, astronauts could receive a sustained supply of formoterol from an implant under their skin. Nanofluidic delivery would help them to avoid a spike in drug levels in their system, meaning they would be able to bypass the negative cardiac side effects and simply sit back and reap the rewards.
Back on Earth, the drug delivery system has a significant potential for patients affected by muscle atrophy due to ongoing health conditions. For those who are bedridden or immobile, an implanted device like this could be life changing.
Grattoni also sees applications for the device outside of formoterol delivery for muscular atrophy.
“Implants can resolve the issues associated with poor adherence to treatment and significantly improve the quality of life of patients,” he says. “Potential applications include treatment and prevention of infectious diseases such HIV, obesity and metabolic syndrome, pain management, drug abuse, mental disorders, hormone replacement and cancer immunotherapy, to name a few.”
Implantable drug delivery systems for HIV-preventing drugs or pain management medications sound almost science fiction, but similar systems are already in active use today. While it uses a different mechanism of action to the nanofluidic system developed at Houston Methodist Research Institute, one of the most popular methods of hormonal birth control is the contraceptive implant, which releases etonogestrel to prevent pregnancy in the user for up to three years. When you look at it that way, it doesn’t seem so unusual.
Grattoni’s, however, is still aiming for the stars.
“While there are ample opportunities for medical application on-Earth, especially for the management of chronic diseases, I believe that implants may one day serve as important tools in space medicine,” he says.