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A novel chitosan-based doxepin nano-formulation for chemotherapy-induced oral mucositis: a randomized, double-blinded, placebo-controlled clinical trial

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Abstract

Objectives

Considering the prevalence of oral mucositis, we aimed to use the analgesic effects of doxepin with chitosan’s antimicrobial and bio-adhesive nature to fabricate a nano-formulation for treating chemotherapy-induced oral mucositis.

Materials and methods

Nanogel was fabricated via ionic gelation and characterized. Sixty patients were randomly divided and received four different treatments for 14 days: diphenhydramine + aluminum–magnesium mouthwash (control), doxepin mouthwash (DOX MW), chitosan nanogel (CN), and doxepin/chitosan nanogel (CN + DOX). Lesions were assessed with four indices, National Cancer Institute (NCI), World Health Organization (WHO), World Conference on Clinical and Research in Nursing (WCCNR) and visual analog scale (VAS) before and 3, 7, and 14 days after interventions. Kruskal–Wallis test was used for pairwise comparison.

Results

CN had semisolid consistency, uniform spherical shape, an average size of 47.93 ± 21.69 nm, and a zeta potential of + 1.02 ± 0.16 mV. CN + DOX reduced WHO, WCCNR, and VAS scores significantly more than the control three days after the intervention. Seven days after the intervention, CN + DOX reduced NCI and WCCNR considerably more than the control; it reduced WCCNR significantly more than CN. Fourteen days after the intervention, CN + DOX decreased NCI markedly more than the control.

Conclusion

Chitosan-based doxepin nano-formulation might be a promising alternative for routine treatments of oral mucositis.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

With this, we gratefully acknowledge the participants in this study, the vice chancellor for research of Shiraz University of Medical Sciences, Daroo Pakhsh Co., for providing us with doxepin powder, and Dr. Vosough, who helped us with the statistical analysis of this project.

Funding

This study was funded by the vice chancellor for research of Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

    Nazafarin Samiraninezhad

  2. Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

    Mostafa Rezaee & Maryam Mardani

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ahmad Gholami

  4. Department of Pediatrics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Amanati

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  1. Nazafarin Samiraninezhad
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  2. Mostafa Rezaee
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  5. Maryam Mardani
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Contributions

M.R. and M.M. contributed to the conception, study design, and critically revised the manuscript. A.G. contributed to the conception, study design, formulation preparation, and critically revised the manuscript. N.S. contributed to data acquisition and interpretation, and wrote the main manuscript, and A.A. contributed to study design and data acquisition. All authors were aware of all parts of the study, gave their final approval, and agreed to be held accountable for all aspects of the work.

Corresponding authors

Correspondence to Mostafa Rezaee or Ahmad Gholami.

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Conflict of interest

All authors declare that they have no competing interests, personal or financial relationships that could have affected the results of this study.

Ethical approval

The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, and the Ethical Committees of Shiraz University of Medical Sciences approved the study by ethical code IR.SUMS.DENTAL.REC.1400.085 and clinical trial code IRCT20110428006322N4. Written consent was taken from participants.

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Samiraninezhad, N., Rezaee, M., Gholami, A. et al. A novel chitosan-based doxepin nano-formulation for chemotherapy-induced oral mucositis: a randomized, double-blinded, placebo-controlled clinical trial. Inflammopharmacol 31, 2411–2420 (2023). https://doi.org/10.1007/s10787-023-01325-7

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  • DOI: https://doi.org/10.1007/s10787-023-01325-7

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