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Simvastatin-loaded nano-niosomes confer cardioprotection against myocardial ischemia/reperfusion injury

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Abstract

Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system. Hence, this study aims to investigate therapeutic efficacy of SIM-loaded nano-niosomes on MI/R injury. Surface active agent film hydration method was used to synthesize nano-niosomes. The physicochemical properties of nano-niosomes were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, niosomes were characterized in entrapment efficiency (EE) and releasing pattern. Male Wistar rats were assigned into five groups (sham, MI/R, SIM, nano-niosomes, and SIM-loaded nano-niosomes). To induce MI/R, left thoracotomy was performed along mid-axillary line. The LAD ligation lasted for 45 min. A single dose (3 mg/kg) of drug formulations was injected into myocardial. Echocardiography was performed to evaluate cardiac function. The expression of the necroptosis markers was evaluated using western blot assay. Particle size of only nano-niosomes was about 137 nm, whereas a shift to 163 nm was observed in nano-niosomes containing SIM. Optimized niosomes were achieved by span 80, drug to cholesterol ratio of 0.4 with 7-min sonication time. EE of optimized nano-niosomes containing SIM was 98.21%. The effects of nano-niosomes containing on improving cardiac function and inhibiting necroptosis pathway was more efficient than the SIM group. Our findings have suggested that nano-niosomes can be applied as a notable drug delivery method to augment stability, bioavailability, and therapeutic efficacy of SIM, when it used against myocardial I/R injury.

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All datasets generated are available on request.

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Acknowledgements

Present work was funded by a research grant from Physiology Research Center in Iran University of Medical Science.

Funding

Present work was funded by a research grant from Physiology Research Center in Iran University of Medical Science.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Maryam Naseroleslami

  2. Department of Medical Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Neda Mousavi Niri

  3. Department of Chemical and Petrochemical Engineering, Sharif University of Technology, 145888-9694, Tehran, Iran

    Iman Akbarzade

  4. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Masoomeh Sharifi & Nahid Aboutaleb

  5. Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Masoomeh Sharifi & Nahid Aboutaleb

Authors
  1. Maryam Naseroleslami
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  2. Neda Mousavi Niri
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  3. Iman Akbarzade
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  4. Masoomeh Sharifi
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  5. Nahid Aboutaleb
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Contributions

I.A. produced and characterized simvastatin-loaded nano-niosomes. Experiments were performed and analyzed by M.N., N.M., and M.SH. Study design, data interpretation, and writing of the manuscript were done by N.A. and M.N. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Nahid Aboutaleb.

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Ethics approval and consent to participate

All the experiments were performed in accordance the ethical standards of the institutional and/or national research committee (ethical number: IR.IUMS.REC.1398.625) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The authors declare no competing interests.

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Naseroleslami, M., Niri, N.M., Akbarzade, I. et al. Simvastatin-loaded nano-niosomes confer cardioprotection against myocardial ischemia/reperfusion injury. Drug Deliv. and Transl. Res. 12, 1423–1432 (2022). https://doi.org/10.1007/s13346-021-01019-z

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  • DOI: https://doi.org/10.1007/s13346-021-01019-z

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