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Cholecalciferol-load films for the treatment of nasal burns caused by cauterization of the hypertrophied inferior turbinate: formulation, in vivo study, and clinical assessment

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Abstract

Nasal turbinate hypertrophy is among the most common nasal obstruction disorders, affecting the patient’s quality of life significantly. Endoscopic submucosal diathermy is a prevalent cauterization procedure for treating turbinate hypertrophy. Regrettably, the nasal burn associated with diathermy typically heals slowly causing facial pain and nasal bleeding and possibly resulting in synechiae formation. In the current study, we have developed, for the first time, a polymeric film loaded with cholecalciferol for local treatment of nasal burns. The casting method was used to prepare films of different compositions of polymers such as chitosan, polyvinyl alcohol (PVA), Carbopol 971p (CP971p), and hydroxypropyl methylcellulose (HPMC) as well as a plasticizer. Several characterizations were performed for the cholecalciferol-loaded films (e.g. weight, thickness, content uniformity, surface pH, folding endurance, disintegration time, and in vitro release) to select the optimal formulation. The optimal formulation (F4) displayed compatibility between the used polymers and the drug. In vivo animal study was carried out to assess the healing efficacy of the formulated cholecalciferol-loaded film. The rabbits treated with the cholecalciferol-loaded film demonstrated significantly higher mRNA expression of the growth factor TGF-β and significantly lower mRNA expression of the proinflammatory cytokine TNF-α and IL-1β compared to the plain film treated group and the untreated control group. A randomized, single-blinded, parallel, controlled clinical trial was conducted on 20 patients scheduled to undergo endoscopic submucous diathermy. The results of the clinical study demonstrated significant reductions in facial pain and nasal bleeding scores for the nostrils treated with cholecalciferol-loaded films in comparison to the nostrils treated with plain films. Furthermore, the endoscopic examination showed good healing for 95% of the cholecalciferol-loaded film-treated nostrils. In conclusion, the optimized film can be considered an opportune approach for enhancing the healing rate of nasal burns and thus reducing the downsides of the diathermy procedure.

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Data availability

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

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Authors and Affiliations

  1. Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Minya, Egypt

    Soad A. Mohamad

  2. Department of Otorhinolaryngology, Faculty of Medicine, Minya University, Minya, Egypt

    Ahmed M. Badwi

  3. Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minya, Egypt

    Mahmoud Elrehany

  4. Department of Biochemistry, Faculty of Pharmacy, New Valley University, New Valley, Egypt

    Sherif Ali

  5. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Deraya University, Minya, Egypt

    Abdelrahman M. Helmy

  6. Pharmaceutical Engineering and 3D Printing (PharmE3D) Lab, Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA

    Abdelrahman M. Helmy

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  1. Soad A. Mohamad
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  4. Sherif Ali
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Contributions

All authors contributed to the study conception and design. Film preparation and characterization were performed by Abdelrahman M. Helmy and Soad A. Mohamad. The animal study and the biochemical assays were conducted by Mahmoud Elrehany and Sherif Ali. Clinical study design and patients’ data collection and analysis were conducted by Soad A. Mohamad and Ahmed M. Badwi. Surgery procedure and patients’ following up were carried out by Ahmed M. Badwi. All authors shared in the production of first draft of the manuscript. The final version of the manuscript was edited and supervised by Abdelrahman M. Helmy and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Abdelrahman M. Helmy.

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Ethics approval and consent to participate

This research was carried out in accordance with the Helsinki Declaration’s principles. The Ethics Committee of Deraya University granted approval (March 3, 2021. /No.2/2021). The clinical trial protocol was registered as NCT05142072 on clinicaltrials.gov. Twenty patients between the ages of 20 and 50 who visited the ENT department were encouraged to take part in the study. Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Figs. 6 and 7.

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The authors declare no competing interests.

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Mohamad, S.A., Badwi, A.M., Elrehany, M. et al. Cholecalciferol-load films for the treatment of nasal burns caused by cauterization of the hypertrophied inferior turbinate: formulation, in vivo study, and clinical assessment. Drug Deliv. and Transl. Res. 13, 1102–1115 (2023). https://doi.org/10.1007/s13346-022-01275-7

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