Specialized Synthetic Medicines for Deep Space Missions

Tooba Tahir

Introduction

The field of synthetic space medicine is gaining increasing attention due to the unique challenges posed by the space environment for the healthcare of astronauts. Space travel exposes astronauts to a variety of environmental stressors, including microgravity, radiation, and altered atmospheric pressure, which can lead to significant physiological changes in the body. These changes can alter the absorption, distribution, metabolism, and excretion of drugs, leading to potential adverse effects or reduced efficacy.

One of the advantages of synthetic space medicine is that it can mitigate the challenge of pharmaceutical expiry during long-duration space missions. Traditional drug synthesis methods rely on natural compounds with limited shelf life and can degrade over time. By using synthetic chemicals instead, it is possible to manufacture pharmaceuticals with extended stability and shelf life, reducing the need for frequent resupply missions to replenish medical stocks.

RIDGE: A Broader Classification Of Space Flight Hazards

Spaceflight hazards can be distributed into 5 distinct categories, summarized with the acronym “RIDGE”: Space Radiation, Isolation and Confinement, Distance from Earth, Gravity fields, and Hostile/Closed Environments, which result in health conditions such as cardiovascular disease, decreased bone density, drop in red blood cell count, and tumours caused by uncontrolled exposure to radiations. So, in order to prevent, cure and treat such diseases specialized medicines are being designed and synthesized.

Preventing Damage To Microbes And Medicines In Outer Space

Space radiation induces accelerated 'Microbial Expiry' and 'Pharmaceutical Expiry’ that could be counteracted with the help of two possible scenarios:

I) 'Microbial expiry' could be prevented by storage in small lead-lined containers while inactive which provides a feasible means of supplementing a microorganism’s natural ability to withstand the harsh environmental conditions in space

II) 'Pharmaceutical Expiry' could be prevented with help of on-site or on-demand synthesis of drugs while onboard. This involves sending the blueprint of the organic chemical from the earth to spacecraft on a deep-space mission followed by the synthesis of drugs with the help of Chemputer - a Universal chemical synthesis robot. In case a new drug is developed on Earth, crewmembers on a space mission could download the computer code for the new molecule and create it on-board

Promising Solutions

Synthetic biology aims to re-engineer organisms (such as plants and other microorganisms) to produce high-value products such as bioplastics, biosensors, protein therapeutics, biofuels, and other bio-inspired materials and to transform microorganisms to serve as biofactories bringing new opportunities for manufacturing biological drugs.

• Following the synthesis of raw pharmaceutical ingredients, active excipients are mixed and fabricated into a dosage form suitable for administration to patients.

• Three-dimensional printing (3DP) technology is utilized for the point-of-care fabrication of personalized medicines.

• Quality control testing could be done with the help of faster, more reliable and portable devices such as Raman spectroscopy which measures drug degradation rate which is further followed by deciding drug dosage form (solid, powder) and the adaptation of a particular drug depot system that slowly releases drug in the body.

3-D Printing - A Promising Tool For On-Site Pharmaceutical Manufacturing In Space

Three-dimensional printing (3DP) has been explored for point-of-care fabrication of personalized medicines in space through NASA's In-Space Manufacturing project. This technology has already been used on the International Space Station (ISS) to create spare parts and medical supplies. Material extrusion-based technologies such as fused deposition modelling (FDM), semi-solid extrusion (SSE), and direct powder extrusion (DPE) have shown promise for pharmaceutical applications in space. Smaller, lighter, and more efficient 3D printers have been developed or planned to comply with Good Manufacturing Practice (GMP) requirements for pharmaceutical production.

Vat photopolymerization, such as stereolithography and digital light processing, which utilize light to solidify liquid resin layer-by-layer, may also be suitable for extraterrestrial applications. Advances in light-induced additive manufacturing techniques have led to the development of volumetric 3D printers, which can achieve higher resolutions and complex geometries in seconds. Exploiting natural resources on other planets and developing recycling technologies for materials could also enable autonomous on-site pharmaceutical manufacturing in space.

Synthetic Drug Delivery Devices

Powder bed fusion technologies, such as selective laser sintering (SLS) and laser beam melting (LBM), have been tested in microgravity conditions for potential deployment in space. Studies have shown that 3D printing with powdered materials can be successfully performed in microgravity, which is important for utilizing regolith (sand-covered planets such as Mars) as a feedstock for manufacturing components, spare parts, and tools. This technology can also be used for fabricating drug delivery devices, such as gastric retentive devices, patches, bandages, bladder devices, suppositories, and microneedle patches, that can be drug-loaded to treat injuries and wounds on-site during space missions.

Synthetic Based Drug Synthesis

Furthermore, 3D printing has the potential to revolutionize the production of medicines in space. By synthesizing drug molecules using techniques like Chemputing or synthetic biology, and then incorporating them into suitable pharmaceutical forms using 3D printing, a drug manufacturing system that is almost independent of Earth resources could be achieved. This could enable the on-demand production of drugs during space missions, eliminating issues related to expiration dates and instability of pharmaceuticals stored on board. However, these technologies would need to be fully integrated into an automatic or semi-automatic platform to account for the limited number of personnel on board to operate them.

Synthetic Functional Cell-Laden Structures

Moreover, advancements in bioprinting have the potential to create complex, fully functional cell-laden structures, such as skin, ears, corneas, organs, and functional living structures, which could be useful in accidents and emergency surgeries during space missions. Bioprinting could also be used for preclinical studies involving animals in the International Space Station (ISS), where 3D printed dosage forms adapted in size and dose to small animals, such as mice, could be manufactured and administered for evaluating drug pharmacokinetics and pharmacodynamics under microgravity and high radiation conditions.

In summary, 3D printing has a wide range of applications in space, including manufacturing components, spare parts, and tools, fabricating drug delivery devices, producing medicines on demand, creating wearable electronic devices and personalized foods, and advancing bioprinting for tissue and organ fabrication. Continued advancements in 3D printing and related technologies have the potential to significantly impact space exploration and enable long-duration space missions with enhanced safety and welfare of crew members.

Fig. 1. On-site production of medicines in space (Seoane-Via˜no et al., 2021)

NASA's SynBio Project

The BioNutrients experiment is part of NASA’s SynBio project (launched in April 2019) that uses genetically-engineered baker’s yeast and an extended shelf-life growth substrate in order to produce specific antioxidants, such as beta carotene and zeaxanthin, typically found in bell peppers, carrots and other vegetables. The BioNutrient packs are filled with dehydrated yeast and their food source. To initiate the tests on a spaceflight sterile water is added to the pack, mixed well, and kept warm for 48 hours. Then the packet is frozen in order to be analyzed later, back on Earth. NASA scientists will then check how the system performed in space, including how much yeast grew in the packets and how much nutrients are produced as a result of microbial growth.

References:

NASA, 2019a. 5 Hazards of Human Spaceflight [Internet]. Available from: https://www.nasa.gov/hrp/5-hazards-of-human-spaceflight (last accessed 30 May 2020).

Venkateswaran K, La Duc MT, Horneck G.2014 Microbial existence in controlled habitats and their resistance to space conditions. Microb.Environ. 29, 243– 249. (doi:10.1264/jsme2.ME14032) University of Glasgow, 2018. ’Chemputer’ Promises App-Controlled Revolution for Drug Production [Internet]. Available from: https://phys.org/news/2018-11-chemputerapp-controlled-revolution-drug-production.html (last accessed 30 May 2020).

El Karoui, M., Hoyos-Flight, M., Fletcher, L., 2019. Future trends in the synthetic biology-a report. Front. Bioeng. Biotechnol. 7, 175.

Seoane-Viãno, I., Trenfield, S.J., Basit, A.W., Goyanes, A., 2021. Translating 3D printed pharmaceuticals: from hype to real-world clinical applications. Adv. Drug Deliv. Rev.174, 553–575.

NASA, 2020b. Space Synthetic Biology (SynBio)[Internet]. Available from: https://www.nasa.gov/directorates/spacetech/game_changing_development/projects/SynBio