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Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments

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Abstract

We aimed to perform a comprehensive study on the development and characterization of silymarin (Syl)-loaded niosomes as potential drug delivery systems. The results demonstrate significant novelty and promising outcomes in terms of morphology, size distribution, encapsulation efficiency, in vitro release behavior, free energy profiles of Syl across the niosome bilayer, hydrogen bonding interactions, antimicrobial properties, cytotoxicity, and in vivo evaluations. The physical appearance, size, and morphology assessment of free niosomes and Syl-loaded niosomes indicated stable and well-formed vesicular structures suitable for drug delivery. Transmission electron microscopy (TEM) analysis revealed spherical shapes with distinct sizes for each formulation, confirming uniform distribution. Dynamic light scattering (DLS) analysis confirmed the size distribution results with higher polydispersity index for Syl-loaded niosomes. The encapsulation efficiency of Syl in the niosomes was remarkable at approximately 91%, ensuring protection and controlled release of the drug. In vitro release studies showed a sustained release profile for Syl-loaded niosomes, enhancing therapeutic efficacy over time. Free energy profiles analysis identified energy barriers hindering Syl permeation through the niosome bilayer, emphasizing challenges in drug delivery system design. Hydrogen bonding interactions between Syl and niosome components contributed to energy barriers, impacting drug permeability. Antimicrobial assessments revealed significant differences in inhibitory effects against S. aureus and E. coli. Cytotoxicity evaluations demonstrated the superior tumor-killing potential of Syl-loaded niosomes compared to free Syl. In vivo studies indicated niosome formulations’ safety profiles in terms of liver and kidney parameters compared to bulk Syl, showcasing potential for clinical applications. Overall, this research highlights the promising potential of Syl-loaded niosomes as effective drug delivery systems with enhanced stability, controlled release, and improved therapeutic outcomes.

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Funding

Kerman University of Medical Sciences financially supported the current study (Project No. 400000994). Additional in vivo examinations were funded by a grant from the University of Zabol (UOZ-GR-1821).

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Authors and Affiliations

  1. Basic Veterinary Science Department, Veterinary Faculty, University of Zabol, P. O. Box. 98613-35856, Zabol, Iran

    Mohammad Reza Hajinezhad

  2. Department of Chemistry, Faculty of Sciences, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran

    Maryam Roostaee

  3. Department of Physical & Computational Chemistry, Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran

    Zahra Nikfarjam

  4. Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, 7616913555, Iran

    Sanaz Rastegar & Mahmood Barani

  5. Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran

    Ghasem Sargazi

  6. Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran

    Saman Sargazi

  7. Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Saman Sargazi

Authors
  1. Mohammad Reza Hajinezhad
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  2. Maryam Roostaee
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  3. Zahra Nikfarjam
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  5. Ghasem Sargazi
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  6. Mahmood Barani
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  7. Saman Sargazi
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Contributions

Mohammad Reza Hajinezhad: conceptualization, methodology, data curation, writing—original draft preparation. Maryam Roostaee: investigation, formal analysis, visualization, writing—reviewing and editing. Zahra Nikfarjam: resources, validation, software. Sanaz Rastegar: validation, investigation, writing—reviewing and editing. Ghasem Sargazi: writing—reviewing and editing. Mahmood Barani: methodology; conceptualization; writing—reviewing and editing; supervision. Saman Sargazi: visualization; data curation; writing—original draft preparation; writing—reviewing and editing. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Mahmood Barani or Saman Sargazi.

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The protocol of the present study was approved by the local ethics committee of Kerman University of Medical Sciences (Ethical code: IR.KMU.REC.1400.678). The webpage for the ethical certificate is available at https://ethics.research.ac.ir/EthicsProposalView.php?&code=IR.KMU.REC.1400.678.

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Hajinezhad, M.R., Roostaee, M., Nikfarjam, Z. et al. Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03099-3

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