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Amelioration of murine experimental colitis using biocompatible cyclosporine A lipid carriers

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Abstract

Lipoproteins are biodegradable and biocompatible natural carriers that can be utilized for the transport of hydrophobic drugs, such as cyclosporin A (CycloA), a calcineurin inhibitor utilized for the inflammatory bowel disease, such as ulcerative colitis. A major limitation in the drug treatment of inflammatory bowel disease is the inability to deliver the drug selectively toward the inflamed tissues. Nanotechnology-based drug delivery systems have led to an amelioration of the therapeutic selectivity, but still the majority of the entrapped drug is eliminated without exercising a therapeutic effect. The present study aimed to prepare three lipoprotein formulations (HDL-, LDL-, and VLDL-based) loaded with cyclosporin A for the treatment of colitis in a murine model. After an intravenous injection of a drug dose of 2 mg/kg, clinical activity (colon weight/length ratio) and therapeutic effects (evaluated by the inflammatory markers MPO and TNF-α) were compared with those of the untreated colitis control group. All CycloA-containing lipoproteins reduced clinical activity, with a significant decrease in the case of LDL-CycloA formulation, which also led to the higher therapeutic effect.

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Data availability

All data generated or analyzed during this study are included in this manuscript.

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Acknowledgments

The authors are grateful to Claire Chrétien for her help during the animal experiments.

Funding

This work is supported by LabEx LipSTIC project, Besancon.

Author information

Author notes

  1. Eleonora Scarcello and Mona M. A. Abdel-Mottaleb contributed equally to this work.

Authors and Affiliations

  1. PEPITE EA4267, Université Bourgogne Franche-Comté, F-25000, Besançon, France

    Eleonora Scarcello, Arnaud Beduneau, Brice Moulari & Yann Pellequer

  2. Department of Drug Science and Technology, University of Turin, Turin, Italy

    Eleonora Scarcello

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Mona M. A. Abdel-Mottaleb

Authors
  1. Eleonora Scarcello
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  2. Mona M. A. Abdel-Mottaleb
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  3. Arnaud Beduneau
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  4. Brice Moulari
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  5. Yann Pellequer
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Contributions

Y.P. proposed the work and designed the experiments. E.S and MM.A.A were responsible for performing the experiments and writing the results. All authors contributed to the discussion and revision of the manuscript.

Corresponding author

Correspondence to Mona M. A. Abdel-Mottaleb.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical conduct of research

The authors state that they have followed the principles outlined in the Declaration of Helsinki for all animal experimental investigations. All animal experiments were approved by the Institutional Animal Care and Use Ethical Committee of the University of Franche-Comté (experimentation authorization number A-25-48) and were carried out in accordance with the approved protocol No 2015-003-CD-12PR. The protocol was designed in accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council, National Academy of Sciences, USA).

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Scarcello, E., Abdel-Mottaleb, M.M.A., Beduneau, A. et al. Amelioration of murine experimental colitis using biocompatible cyclosporine A lipid carriers. Drug Deliv. and Transl. Res. 11, 1301–1308 (2021). https://doi.org/10.1007/s13346-020-00835-z

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