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ORIGINAL RESEARCH

Preparation, characterization, and in vivo evaluation of a fluconazole-loaded chitosan lipid nanoparticle hydrogel in a rat wound model infected with fluconazole-resistant Candida albicans

Rawia M. Khalil1 ,  Marwa A. Wagdi1 ,  Shaymaa A. Ismail2 ,  Amira A. Hassan2 ,  Marwa E. Shabana3 ,  Ahmed A. Sedik4 ,  Eman S. Shalaby1*
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1 Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza, Egypt
2 Department of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza, Egypt
3 Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
4 Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
BMT, 26 https://doi.org/10.12336/bmt.25.00026
Submitted: 9 May 2025 | Revised: 30 December 2025 | Accepted: 7 January 2026 | Published: 16 July 2026
© 2026 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
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Abstract

Fungal infections are among the most serious dermatological disorders and affect more than 25% of the global population. Candida albicans infection is considered the most widespread fungal infection. This research aims to assess the effect of the topical application of fluconazole (FLU) lipid nanoparticles (LNPs) loaded in a chitosan natural biopolymer hydrogel (FLU–LNP–CHI) on a rat wound excision model infected with C. albicans. Four formulations (F1–F4) were chosen based on the encapsulation efficacy findings (ranging from 12.1% to 72.5%). Chitosan biopolymers were used to enhance the antimicrobial effect, viscosity, and industrial applicability of LNPs. The particle size (251.6–409.0 nm) and zeta-potential (22.82–51.73 mV) of the formulations were determined. In the in vitro antifungal study, F2 (zone of inhibition = 23 ± 0.4 mm) showed better antifungal properties than F4 (zone of inhibition = 21 ± 0.7 mm). After several assessments, F2 and F4 were selected for evaluation of their biological effectiveness in healing C. albicans-infected wounds. Histological and in vitro antifungal analyses were used to evaluate the subsequent healing process. The results confirmed that FLU–LMP–CHI can accelerate wound healing by increasing indices of skin regeneration, as evidenced by histopathological studies. Our findings indicate that, compared with FLU alone, FLU–LNP–CHI has significant potential to improve the healing of FLU-resistant C. albicans-infected wounds due to its potent antifungal properties.

Keywords
Fungal infection
Candida albicans
Wound
Chitosan
Fluconazole
Histopathology
Funding
None.
Conflict of interest
The authors have no financial or personal interests that could be perceived as influencing the content of this work.
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