The perpetual need and desire to discover new celestial bodies and colonize them, has led scientists to investigate and explore intensely the secrets of outer space environment. Nevertheless, mapping interstellar dimensions and amplitudes is appeared to be demanding and complicated, due to the unpredictability of Universe’s chaotic systems. Therefore, substantial efforts have been dedicated to identifying and mitigating potential risks associated with enhancing astronauts’ habitability, during spaceflights.

NASA has introduced the acronym “RIDGE” to encompass the most critical hazards astronauts encounter during spaceflight missions: space radiation, isolation and confinement, distance from Earth, gravity fields, and hostile/closed environments [1]. Astronauts are exposed to ionizing radiation, including galactic cosmic rays (GCR) and solar particle events (SPE), whose intensity corresponds to 150 to 6,000 chest x-rays. This exposure affects the integrity of the genome, leading to disruptions of physiological cell functions, thereby increasing the risk of various chronic health issues (e.g., cancer, cardiovascular diseases, cataracts) [2]. The limitation of movements within the spacecraft along with the microgravity environment can cause edema (e.g., puffy face), diminished leg volume (e.g., chicken legs), muscle atrophy, back pain, and bone resorption [3]. Conversely, long-term isolation and confinement disturb astronauts’ circadian rhythms, triggering insomnia, dysregulation of the immune system and inflammations, alterations in the microbiome and gastrointestinal malfunctions [4]. Psychological issues and behavioral shifts, including loss of motivation, anxiety, and depression, can be also manifest during extended space missions. Moreover, microgravity may give rise to several syndromes, such as the space adaptation syndrome (SAS), otherwise space motion sickness (SMS), which is particularly common among the spacecraft crew during the initial days in orbit. Furthermore, astronauts may develop the spaceflight-associated neuro-ocular syndrome (SANS), due to high intracranial pressure [5]. Finally, the endeavor of space trekking brings forth hazards related to celestial body ecosystems, which are harsh and inhospitable to humans, such as pathogenic microorganisms, gases, and space dust [6].
Currently, the provision of medications during space missions is based on prior storage and/or are restocked by cargo delivery; strategies addressed only for short-term stays. The maintenance, the expiration date, and the adequacy of medicines, as well as the administration route and the modified pharmacodynamics, and pharmacokinetic attributes, are critical factors which may impede the efficiency of treatment. Thus, the concept of “on-board” medicinal preparations is being appraised as a possible process for personalized and on “in-house” formulations. Emerging technologies (ET), such as 3D printing (3DP), microfluidic (MF) portable devices, and internet of things (IoT) systems, offer promising avenues for the rapid and on-site composition of raw materials, leading to the creation of final dosage forms. These advancements could revolutionize the process of pharmaceutical production in space, ensuring tailored medical solutions that meet the unique demands of each individual astronaut [8].
The synthesis of composite chemical structures on the International Space Station (ISS), is a procedure that differs from conventional dosage forms development, aiming towards enhancing stability and ensuring a continuous supply of medications throughout space missions. Biological Medication on Demand (Bio-MOD) encompasses a microfluidics-based system, which can be utilized to produce diverse drugs from raw materials; thus, this approach remains smart in its simplicity and practicability, involving feasible steps [9]. Moreover, the use of “moon simulants”, which are inorganic materials detected on the moon surface, could be efficient excipients for the fabrication of various pharmaceutical dosage forms; hence, a sustainable, energy-efficient, and cost-effective method, in terms of long-distant missions [10].
3DP holds significant promise as a technique that can be harnessed to prepare tailor-made medicines and even food to address specific remedies or nutritional element substitution for the well-being of space travelers. Notably, within the realm of 3DP, VAT photopolymerization printers (e.g., stereolithography (SLA), direct light processing (DLP), continuous liquid interface production (CLIP) 3DP) exhibit the potential to swiftly and precisely create uniform and high-resolution structures, powder bed fusion (PBF) technologies, such as selective laser sintering (SLS) and Laser Beam Melting (LBM) printers, could be implemented under zero gravity conditions, aiming towards the use of powder-based materials, while bioprinting could find application in generating cell-laden structures. Therefore, 3DP emerges as a versatile tool for the fabrication of a broad variety of formulations, such as multi-active pharmaceutical ingredient (API) printlets, microneedle patches, ocular lenses, and antimicrobial bandages, among other types of dosage forms, described by diverse release profiles, shapes, and sizes [8].

Nowadays, humans have achieved to undertake long and far space missions, akin to the interstellar escapades portrayed in films such as Star Trek and Star Wars. As famously stated by Dr Spock, “Insufficient facts always invite dangers”, traveling along space and seeking new human-viable intergalactic ecosystems hide various risks and challenges, which are difficult to be predicted or controlled. The application of artificial intelligence (AI) systems in technological advancements, capable of forecasting and estimating the variability of factors that affect the safety of space flights, is currently in the research and development phase. Therefore, a consensual regulatory framework regarding the application of ET for the development of medicines under Good Manufacturing Practice (GMP) regulations remains a constant hassle.
Although the exploration of intergalactic space lurks a lot of unforeseen incidences, it steadfastly remains a challenging and exhilarating adventure for humanity – one that is poised and prepared to delve into the depths of the Universe, uncovering its enigmatic mysteries.
References:
NASA, 2019a. 5 Hazards of Human Spaceflight [Internet]. Available from: https://www.nasa.gov/hrp/5-hazards-of-human-spaceflight. (Accessed 14 August, 2023).
NASA, 2019. Why Space Radiation Matters [Internet]. Available from https://www.nasa.gov/analogs/nsrl/why-space-radiation-matters. (Accessed 14 August, 2023).
Lee, A.G.; Mader, T.H.; Gibson, C.R.; et al. Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update. npj Microgravity. 2020, 6 (7). DOI: 10.1038/s41526-020-0097-9.
Low, L. A.; Giulianotti, M. A. Tissue Chips in Space: Modeling Human Diseases in Microgravity. Pharm. Res. 2020, 37 (1), 8.
Hodkinson, P.D.; Anderton, R.A.; Posselt, B.N.; Fong, K.J. An overview of space medicine. Br. J. Anaesth. 2017, 119, i143–i153.
Borisova, T. Express assessment of neurotoxicity of particles of planetary and interstellar dust. npj Microgravity. 2019, 5 (1), 2.
Tran, Q.D.; Tran, V.; Toh, L.S.; et al. Space Medicines for Space Health. ACS Med Chem Lett. 2022, 13, 1231–1247.
Seoane-Viaño, I.; Ong, J.J.; Basit, A.W.; et al. To infinity and beyond: Strategies for fabricating medicines in outer space. Int J Pharm X. 2022, 4, 100121.
Steiner, S.; Wolf, J.; Glatzel, S.; Andreou, A.; Granda, J.M.; Keenan, G.; Hinkley, T.; Aragon-Camarasa, G.; Kitson, P.J.; Angelone, D.; Cronin, L. Organic synthesis in a modular robotic system driven by a chemical programming language. Science. 2019, 363, eaav2211.
Tran, Q. D.; Tran, N.; Hessel, V.; Thavarajah, S. R.; Rahman, S.; Stoudemire, J.; Zeckovic, O.; Fisk, I. Long-duration stability study of medicines on the International Space Station providing data for potential future on-orbit manufacturing, 43rd COSPAR Scientific Assembly. 2021, p 1835.
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