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Application of a Thermosensitive In Situ Gel of Chitosan-Based Nasal Spray Loaded with Tranexamic Acid for Localised Treatment of Nasal Wounds

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Abstract

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5 min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.

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Author notes

  1. Hanieh Gholizadeh and Elisa Messerotti contributed equally to this work.

Authors and Affiliations

  1. School of Engineering, Macquarie University, Sydney, Australia

    Hanieh Gholizadeh & Shaokoon Cheng

  2. Respiratory Technology, Discipline of Pharmacology, Faculty of Medicine and Health, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia

    Hanieh Gholizadeh, Elisa Messerotti, Michele Pozzoli, Daniela Traini, Paul Young & Hui Xin Ong

  3. Department of Drug Sciences, University of Pavia, Pavia, Italy

    Elisa Messerotti & Carla Caramella

  4. School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, Australia

    Agisilaos Kourmatzis

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  1. Hanieh Gholizadeh
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  2. Elisa Messerotti
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Correspondence to Hui Xin Ong.

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Gholizadeh, H., Messerotti, E., Pozzoli, M. et al. Application of a Thermosensitive In Situ Gel of Chitosan-Based Nasal Spray Loaded with Tranexamic Acid for Localised Treatment of Nasal Wounds. AAPS PharmSciTech 20, 299 (2019). https://doi.org/10.1208/s12249-019-1517-6

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