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New Approach to Formulate Methotrexate-Loaded Niosomes: In Vitro Characterization and Cellular Effectiveness

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Abstract

Purpose

Methotrexate is one of the widely used agents to treat various solid tumors, although its usage brings some challenges because of its poor bioavailability and/or dose-dependent side effects. Increasing the solubility, permeability, and consequently bioavailability in company with minimizing side effects are always desired to formulate such these drugs. In this paper, we concentrated on formulation parameters of methotrexate-loaded niosomes, in an attempt to facilitate its solubility.

Methods

Various formulation parameters were utilized, including surfactant types, the amount of membrane additives, and types of hydrating agent. Methotrexate-loaded niosomes were fully characterized. The cell viability and hemolysis assay were evaluated. The effects of developed formulation on cellular interaction, growing, and micronuclei assay were also investigated.

Results

Methotrexate (MTX)-loaded niosomes were produced in small particle size (241.3 ± 65.7 nm) with high uniformity using sodium hydroxide as hydrating solution. Their entrapment efficiency was 59.5 ± 3.0% and the release completed in 6 h. The incorporation of methotrexate into niosomes was confirmed, and their higher efficiency on cell viability was presented. MTX-loaded niosomes were found safe and acceptable for parenteral administration. The number of apoptotic and dead cells were increased significantly in all types of cells treated with niosomes. The apoptosis-mediated cell death was triggered by produced niosomes.

Conclusion

This study suggests that MTX-loaded niosomes formulated with sodium hydroxide provided a significant improvement in niosome characteristics with the help of solubility enhancement strategies. The cellular assessments proved its potential efficacy. It is concluded that these promising results should be promoted in further studies.

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Acknowledgements

The corresponding author would like to thank Yildiz Technical University, Scientific and Technological Application and Research Centre, where the SEM images were taken, and also to thank Selcuk Birdogan at Acıbadem University for TEM imaging studies.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Biruni University, Zeytinburnu, 34010, Istanbul, Turkey

    Gulen Melike Demirbolat

  2. Department of Pharmaceutical Technology, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Gulen Melike Demirbolat

  3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Tandogan, 06100, Ankara, Turkey

    Ezgi Aktas

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Acıbadem University, 34684, Istanbul, Turkey

    Goknil Pelin Coskun

  5. Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, 09010, Aydin, Turkey

    Omer Erdogan & Ozge Cevik

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  1. Gulen Melike Demirbolat
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Demirbolat, G.M., Aktas, E., Coskun, G.P. et al. New Approach to Formulate Methotrexate-Loaded Niosomes: In Vitro Characterization and Cellular Effectiveness. J Pharm Innov 17, 622–637 (2022). https://doi.org/10.1007/s12247-021-09539-4

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