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Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects

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Abstract

Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was < 250 nm, and HC-HT CSNPs AQ cream remained stable when stored at 25 °C. TEWL and erythema intensity for 28-day application did not indicate any signs of local irritation, redness, and toxicity, which were confirmed by normal Draize skin irritation scoring system and skin hematoxylin and eosin (H&E) staining results. Comparative results of blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone level at day 0 and day 28 were not significant, indicating non-systemic toxicity. In conclusion, HC-HT CSNP AQ cream is safe, well-tolerated, and non-toxic, which may be useful in treating atopic dermatitis.

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Acknowledgments

The authors would like to thank the participants, investigators, and investigational site, whose participation made this study possible.

Funding

The authors gratefully acknowledge the financial support provided by the Universiti Kebangsaan Malaysia (UKM-AP-2013-002) for conducting this study.

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Authors and Affiliations

  1. Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Muhammad Irfan Siddique, Haliza Katas, Mohd Cairul Iqbal Mohd Amin, Shiow-Fern Ng & Mohd Hanif Zulfakar

  2. Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan

    Muhammad Irfan Siddique

  3. Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    Adawiyah Jamil

  4. Department of Pathology, University of Veterinary and Animal Sciences, Lahore, Pakistan

    Syed Maaz Nadeem

Authors
  1. Muhammad Irfan Siddique
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  2. Haliza Katas
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  3. Adawiyah Jamil
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  4. Mohd Cairul Iqbal Mohd Amin
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  5. Shiow-Fern Ng
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  6. Mohd Hanif Zulfakar
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  7. Syed Maaz Nadeem
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Corresponding author

Correspondence to Haliza Katas.

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The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Research Ethics Committee of the National University of Malaysia (UKM FPR.4/244/FF-2015-275). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Siddique, M.I., Katas, H., Jamil, A. et al. Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects. Drug Deliv. and Transl. Res. 9, 469–481 (2019). https://doi.org/10.1007/s13346-017-0439-7

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  • DOI: https://doi.org/10.1007/s13346-017-0439-7

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