Improving melatonin drug delivery through nanoscale techniques

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The use of nanotechnology in melatonin-based therapeutic agents to treat several disorders was examined in a study published in international cancer cell.

Study: Nanotechnology-Based Advances in the Effective Delivery of Melatonin. Image Credit: Vikks/Shutterstock.com

Melatonin

melatonin, or NOT-[2-(5-methoxy-1H-indol-3-yl) ethyl], is a biogenic amine that is generated primarily by the pineal gland. Its wide range of biological functions, from insomnia to cancer and degenerative disorders, has illustrated its potential as a highly effective therapeutic agent.

Figure 1. The schematic illustrations provided show melatonin and selenium based nanoparticles and their effects. © Mirza-Aghazadeh-Attari, M., Mihanfar, A., Yousefi, B. and Majidinia, M., (2022).

However, due to melatonin affecting cell membrane receptors in the nucleus, it may act as an antioxidant molecule with adverse effects seen after administration.

Interestingly, advancements in drug delivery through the use of nanotechnology would allow melatonin to be delivered more safely and efficiently.

The use of nano-delivery systems that transport melatonin ensures an increase in half-life as well as a decrease in toxicity. Additionally, the use of nanocarriers provides a biodegradable and efficient delivery mode that can improve the pharmacokinetic interactions of melatonin as a therapeutic agent, with better patient compliance due to its high efficacy.

Using melatonin as a therapeutic agent in this way allows for enhanced targeting of cellular pathways due to its delivery to specific areas, increasing the effectiveness of this hormone in the target organ and reducing systemic side effects on tissues. peripheral devices.

Nanotechnology-Based Drug Delivery Systems

Research into new drug delivery systems has included the use of nanotechnology and biomaterials and increased the effectiveness of drugs, advancing the use to deliver melatonin in a more efficient approach.

Nanoparticles that are at the nanoscale of 1 and 100 nm can consist of a range of biodegradable components including polymers, lipids, metals, etc.

The use of these nanocarriers may prove useful due to the natural interaction with biological systems, allowing for efficient selectivity and delivery and ultimately increasing therapeutic outcomes.

Selenium

Selenium, an essential trace element, used to build selenoproteins that have high enzymatic activity, has been used to create nanoparticles (SeNPs).

These particles have shown significant anti-cancer effects, with research into their use as a monotherapy as well as a combination therapy to be used as a nanodrug delivery system for cancer therapy.

Interestingly, the incorporation of melatonin and SeNPs exemplified beneficial synergy, with a combination of the two agents resulting in a significant reduction in immune response damage followed by administration of BCG (Bacillus Calmette-Guerin) to liver cells. in mice.

This combination treatment that used melatonin was also found to reduce the adverse effects of reactive oxygen species (ROS) after exposure to BCG in a separate study.

The schematic diagram provided reveals chitosan melatonin nanostructures and its functions

Figure 2. The schematic diagram provided reveals chitosan melatonin nanostructures and its functions. © Mirza-Aghazadeh-Attari, M., Mihanfar, A., Yousefi, B. and Majidinia, M., (2022).

Chitosan

The significant reduction in DNA damage and ROS formation can also be seen with previous research using chitosan nanoparticles as a nano-drug delivery system that delivers melatonin to HepG2 cancer cells.

These cancer cells were treated with etoposide, a genotoxic topoisomerase II inhibitor, and the purpose of including melatonin was to assess its beneficial effect in reducing the damage of cancer treatment.

The most significant results of this research consisted of a group of cells undergoing melatonin treatment 24 hours before receiving etoposide treatment.

Solid lipid nanoparticles

Additionally, research on the pharmacokinetics of melatonin administered through the use of solid lipid nanoparticles (SNLs), which have exceptional penetrating abilities including hydrophobic barriers and the central nervous system, has also revealed an increase in serum levels using this nanotechnology approach.

This technique utilized oral and transdermal administration of this SNL-melatonin complex and resulted in elevated plasma melatonin levels to over 50 pg/ml for approximately 24 hours after administration of only 3 mg of melatonin under this form of nanocarrier.

Translational significance

Because melatonin has a short half-life and is rapidly cleared from the body’s circulatory system, the time it takes to take effect for the treatment of disorders may be ineffective.

Moreover, its limited absorption from mucosal and dermal surfaces is also another challenge for conventional drug delivery systems involving the delivery of melatonin.

Research conducted on the delivery of melatonin via this nanotechnology format has illustrated the potential for increasing its presence in the circulatory system as well as its impact in improving cancer treatments.

Additionally, its use in conventional applications such as insomnia, jet lag, and sleep disorders can be enhanced with sustained delivery through this novel nanotechnology delivery system.

With clinical trials of this hormone for multiple disorders ranging from neoplastic conditions to degeneration, the potential for melatonin in healthcare and medicine may be significant.

However, research on the release of melatonin nanoparticles is still in its infancy with in vitro delivery and models of human conditions; meaningful translation of this research would require further studies that evaluate the safety as well as the cost-effectiveness of human administration.

The figure shows the liposome as a melatonin delivery vehicle, the liposome increases the transdermal delivery of melatonin and also increases the distribution of melatonin to several parts of the body like the cornea as a fragile site

Picture 3. The figure shows the liposome as a melatonin delivery vehicle, the liposome increases the transdermal delivery of melatonin and also increases the delivery of melatonin to several parts of the body like the cornea as a fragile site. © Mirza-Aghazadeh-Attari, M., Mihanfar, A., Yousefi, B. and Majidinia, M., (2022).

Reference

Mirza-Aghazadeh-Attari, M., Mihanfar, A., Yousefi, B. and Majidinia, M., (2022). Advancements based on nanotechnology in the efficient delivery of melatonin. international cancer cell, 22(1). Available at: https://cancerci.biomedcentral.com/articles/10.1186/s12935-022-02472-7

Further reading

Talib, W., Alsayed, A., Abuawad, A., Daoud, S. and Mahmod, A., (2021). Melatonin in the treatment of cancer: current knowledge and future opportunities. Molecules, 26(9), p.2506. Available at: https://doi.org/10.3390/molecules26092506

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