1. INTRODUCTION:

Pharmaceutical products are the integral part of the human being not on earth but in the space also. Pharmacy has a very important role to provide effective medication to astronauts in space travels. The primary purpose of developing space medicine is to put astronauts' health first during manned trips. Staying in an external space environment for an extended amount of time has a variety of impacts on the body, including muscle atrophy, disturbance of the circadian cycle, loss of sleep and appetite, and a general deterioration in mental and physical function.

The main aim behind this review is to give the brief information about the space environment on the astronaut’s health. The information about health problems which are associated with the microgravity. Effects of microgravity on the stability of the drugs, Potential approaches to overcome the stability problems of drugs and to give effective medication to the astronauts. We hope that this review will provides a brief information of the overall scenario in the field of space medication and emerging approaches of formulating them.

2. Space flight environment and its effects on human:

Upcoming space missions would need humans to go beyond the Earth's magnetic field for extended periods of time, exposing them to radiation threats such as solar flares and galactic cosmic rays, as well as changed gravitational fields and physiological stress.¹ In this mission, astronauts lose muscle mass due to microgravity, Moreover, the fluids in the body shift upward to the head in microgravity, which may put pressure on the eyes and cause vision problems. If not prevent than crews developing the risk of kidney stones due to dehydration and increased excretion of calcium from bone.² Factors related to space environment are 1) Acceleration, 2) Weightlessness (microgravity), 3) Cosmic radiation, 4) Extreme uv radiation, 5) High vacuum, 6) Temprature and humidity extremes, 7) Disruption of circadian rhythm, 8) Noise and vibration, 9) Magnetic field produced by the spacecraft's electrical cables, 10) Gaseous material from the intestines that is recycled in the air²

3. Effects of microgravity on human body:

In space, the reduced gravitational force (microgravity) causes physiological changes in the human body, which could compromise medicine safety and efficacy. The duration of these changes varies widely, ranging from immediate resolution within days after arriving at the space centre or shortly after returning to Earth to several years, with some irreversible effects that never fully resolve.³

4. Astronaut-related issues in space:

Astronauts have had a number of consistent medical issues while in space. Vestibular dysfunction, weight loss, height gain, upward fluid shift, anemia, cardiovascular deconditioning, muscular atrophy, and bone loss are only a few of them. The absence of gravitational pull is responsible for almost all of these changes. Most are adaptive and so reversible in nature, however readaptation after returning to Earth may bring additional issues (e.g., in the case of vestibular dysfunction). The persistent bone loss linked with negative calcium balance is the most recalcitrant and distressing of all these issues. After two years in a weightless state, considerable demineralization can manifest, and this condition appears to be irreversible.¹ Another issue is related to the sleep deprivation. Sleep deprivation was common among astronauts not just during space shuttle and ISS flights, but also throughout a three-month preflight training period. Despite on-going sleep loss, sleeping pills were frequently taken while in space. Because persistent sleep deprivation reduces performance, our findings highlight the importance of developing effective sleep- promoting countermeasures.⁴ Other clinical conditions during flight based on the symptoms that astronauts observed are: 1) The most common occurrence was skin rashes, and other infectious diseases were the most often occurring conditions (non-respiratory). 46% of the crew members reported a "notable" incident during the trip, 2) Rashes/hypersensitivities were identified as 40% of the noteworthy events, 3) On-orbit rashes were identified as redness with irritation, and they could appear on any part of the body, 4) Astronauts endure adverse medical events of various severity during long-duration spaceflights, according to reported symptoms.⁵

5. Drug related issues:

The efficacy of space medicine has been a source of contention. According to a report provided by the National Aeronautics and Space Administration (NASA), astronauts took a variety of medications. The drug’s effect was either weaker or absent. A standard dose of medication to cure a headache, for example, did not totally relieve the pain when administered during a space journey. The absorption, distribution, metabolism, and elimination of medications flown in spaceflight may all be affected by changes in human physiology in space. Another reason could be the insufficiency of pharmacological stability in the space environment. Medicines in space flight kits are commercially available and are similar to self-medications used on Earth. They haven’t been tested for use in long-term or short-term space missions. As a result, ensuring the shelf-life of space medicine is critical for long-duration space journeys.⁶

High vacuum, microgravity, temperature extremes, meteoroids, space debris, ionospheric plasma, and ultraviolet and ionizing radiation characterize the environment.⁷ The degree of damage produced by distinct daughter ions to each class of drugs is unknown because investigations of radiation impacts on pharmaceuticals on the ground are not aimed to investigate or estimate the effect of fragmentation ions on stability. In the case of medications, it is critical to determine the structure and biological activity of degradation products, as well as set toxicity limits for active degradants in a formulation, due to concerns about radiation effects that could cause significant changes in the levels of the active pharmaceutical ingredient or the medication’s efficacy. In terms of the therapeutic index of a formulation deteriorated in space, these may suggest a higher risk of toxicity than effectiveness.⁸

6. Technologies in formulation of space medicine:

Newer technologies in the area of pharmaceutical research are being developed daily to address the issues raised above. The section below provided instances of more recent technology.

6.1 Silicon based drug delivery:

In the first approach silicon is the main material which provides long-term constant or pulsatile release of medicines. This has been produced using silicon-based drug delivery devices for the treatment of diseases like hepatitis, cancer, etc.⁹ Several features are provided by porous Si microparticles which make them attractive for regulated medication delivery: First, is their low toxicity which makes them good candidate for various therapeutic application. Second is their propensity to breakdown in the body makes them less problematic for long-term use.¹⁰ Si based material can also be used for the biological products like proteins. For the proteins and other medicines mesoporous silicon based particles can be used to deliver them in controlled and targeted manner.¹¹ Silicon-based nanomaterials can also be used for the construction of novel biocompatible nanotheranostics (nanomaterials for therapy and diagnostics) because it provides wide range of nanomaterial design possibilities, as well as the promising biocompatibility features.¹²

6.2 BioNano Scaffolds (BNS):

BioNano Scaffolds (BNS) are extensively used in the research of tissue regeneration in osteoporosis. Scaffold materials can now be made from natural or synthetic polymers including polysaccharides, poly (a – hydroxy ester), alginate, fibrin, or hyaluronic acid.^13,14 It can promote tissue regeneration regardless of the implantation site or environmental conditions (i.e., this is for the bone, with or without externally applied loads).

Ibuprofen-loaded PLA Nano fibrous scaffolds are another example, which aided in the adhesion and growth of human epidermal keratinocytes and human dermal fibroblasts. Ibuprofen-loaded PLA bandages with cell seeds have been utilized to treat wound contracture and promote blood vessel growth.¹⁵

6.3 Microspheres:

One significant group of stem cells that may develop into osteoblasts, chondrocytes, and adipocytes are mesenchymal stem cells (MSCs). Moreover, MSCs actively contribute to tissue homeostasis maintenance and repair.¹⁶ In the born tissue regeneration process Mesenchymal Stem Cells (MSC), which are precursors to bone-forming osteoblasts, were delivered to the site of damage for the bone growth. Damage to these stem cells during transportation could lead to incomplete or erroneous tissue development. To overcome this calcium alginate microspheres capable of MSC encapsulation and cryopreservation were designed and described in order to assist the safe distribution of MSC within the PPF stabilizing scaffold. In the research cryopreservation Sambu et al. established that alginate encapsulation is a safe and reliable cryopreservation approach.^17,18

6.4 Bioactive glass scaffolds:

Since Hench's discovery of 45S5 bioactive glasses, they've been used as scaffold materials for bone healing on a regular basis. Bioactive glasses have a well- known potential to promote bone cell proliferation and to form strong bonds with both hard and soft tissues. Bioactive glasses undergo certain processes after implantation, which result in the production of an amorphous calcium phosphate (ACP) or crystalline hydroxyapatite (HA) phase on the glass's surface, which is responsible for the glass's strong bonding with the surrounding tissue. Bioactive glasses have also been shown to emit ions that stimulate angiogenesis and activate the expression of osteogenic genes.¹⁹

6.5 Gold Nanoparticles:

Gold nanoparticles (GNPs) are a promising carrier for delivering a variety of payloads to their intended destination. GNPs have been used for multimodality imaging, tumor targeting, and as a transporter of numerous medicines due to their unique physicochemical and optical features. GNPs have also been utilized to treat cancer via photo thermal therapy.²⁰ Gold nanoparticles are less harmful and safe for the treatment of cancer than metallic nanoparticles.^21,22 Au NPs can also be employed as protein delivery nanocarriers. The interfacial contact between protein and Au NPs has substantial consequences for the applications of Au NPs in biology and biomedicine; for example, when Au NPs have been functionalized by chitosan, they can be utilized to deliver insulin.²³

6.6 Nano Glands:

The phrase "Nano-Gland" refers to an implantable medication delivery system that mimics the functions of bodily glands. Nano-Glands capable of tailored hormone and drug release may reduce the need for such a strenuous workout regimen, as well as provide radiation protection through the timed release of a suitable radio protective pharmacological substance.⁹ With feedback loops, a network of biosensing nodes (BSN) connects with the Nano gland. The Nano gland responds to input and controls the release of pharmaceuticals while reporting health status to a monitoring center (MC) via radio frequency.²⁴

6.7 Three Dimensional Printing (3D Printing):

Three-dimensional printing (3DP) has emerged as a promising developing technique with enormous potential in the production of pharmaceuticals using simple and rapid product manufacturing strategies. The use of 3DP in medication delivery, especially space pharmaceuticals, has proven to be a wonderful and incredible method.²⁵ In comparison to traditional approaches, 3DP could aid in the small-scale synthesis of a variety of compounds, which could be especially advantageous for those with high costs or low stability.²⁶

7. Several studies in which 3DP is used for formulating the drugs are given bellow:

Pietrzak and colleagues used the FDM 3DP to develop and print a flexible dosage form of theophylline tablet with immediate and sustained release patterns, increased loading capacity, and ease of ingestion. Because of its highly customizable printing nature, as well as its compact size and ease of use, this approach provides the potential for future individualized therapies.²⁷

Lee et al. created paclitaxel microparticles with controlled and predefined forms using a piezoelectric inkjet printing technology as a simple and easy-to-use approach. The created microparticles released in a two-phased pattern, with an initial burst followed by a steady release. In the study it was found that the release rate was proportional to the microparticles' shape and surface area.²⁸

8. Astropharmacy (A system for making medicines on demand):

Astropharmacy is the novel and immerging approach introduced to provide effective medicines to the astronauts in the space. In other words we can say that Astro pharmacy is the contribution of pharma sector to the space sector.

Because disease is an unavoidable part of life, disease prevention, diagnosis, and treatment will be essential for human deep space missions. Pharmaceuticals are used to diagnose, treat, cure, or prevent disease, but they suffer from a lack of stability on Earth, and this is exacerbated in space. What if drugs in small quantities could be manufactured in space, on-site, and on-demand? The biopharmaceutical or 'biologic' (peptide or protein medications) class of therapies would be particularly conducive to space manufacturing.²⁹

9. CONCLUSION:

Several studies that discussed in this review provides evidence about the effects of microgravity on the astronauts and on the drug. According to anecdotal evidence, changes in physiological indices that occur during spaceflight are most likely to affect astronaut’s health, physiology of the body, drug potency, therapeutic effect, and safety. The medicine kind and formulation, flight duration, and ambient conditions all influence these changes. There is currently inadequate available information on these subjects, necessitating the need for investigations and solutions to be implemented in time to support prospective space missions. The approaches that we implement on the earth can also be used for space medicines.

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Received on 02.01.2023 Modified on 12.04.2023

Research J. Science and Tech. 2023; 15(3):140-144.

DOI: 10.52711/2349-2988.2023.00023