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<p>Fungal and bacterial infections are critical complications in atopic dermatitis (AD), significantly affecting patient quality of life and healthcare outcomes. Luliconazole (LZ), a potent topical broad-spectrum antifungal, inhibits ergosterol biosynthesis but is limited by low water solubility and dermal bioavailability. Metronidazole (MTZ), a nitroimidazole antimicrobial, exhibits robust antibacterial properties and offers potential enhanced antimicrobial benefits when combined with antifungals. This study focuses on the co-crystallization of LZ and MTZ to overcome LZ’s solubility limitations and enhance its therapeutic efficacy in AD. The co-crystals of LZ and MTZ were synthesised and characterized using advanced analytical techniques, including Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Nuclear Magnetic Resonance (NMR) spectroscopy, confirming successful co-crystal formation. A topical cream was subsequently formulated and evaluated for its physicochemical properties, including pH, spreadability, viscosity, and in-vitro release study. The in vitro antimicrobial activity of the formulation was assessed against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Candida albicans</i>, pathogens frequently implicated in secondary infections in AD. Results demonstrated that the co-crystal significantly enhanced the solubility of LZ and exhibited enhanced antifungal and antibacterial effects. The topical cream showed favourable physicochemical attributes and superior antimicrobial activity, positioning it as a promising dual-therapy approach for managing fungal and bacterial infections associated with atopic dermatitis. This novel formulation addresses critical challenges in the treatment of AD, offering a potential improvement in clinical outcomes and patient compliance.</p> Graphical Abstract <p></p>

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Design of Bifunctional Luliconazole–Metronidazole Co-Crystals for Antifungal and Antibacterial Therapy in Atopic Dermatitis

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • C. Nithya Shanthi,
  • Ram Prasad,
  • Deepanshu Rana,
  • Riya Mahar,
  • Arun Mahato

摘要

Fungal and bacterial infections are critical complications in atopic dermatitis (AD), significantly affecting patient quality of life and healthcare outcomes. Luliconazole (LZ), a potent topical broad-spectrum antifungal, inhibits ergosterol biosynthesis but is limited by low water solubility and dermal bioavailability. Metronidazole (MTZ), a nitroimidazole antimicrobial, exhibits robust antibacterial properties and offers potential enhanced antimicrobial benefits when combined with antifungals. This study focuses on the co-crystallization of LZ and MTZ to overcome LZ’s solubility limitations and enhance its therapeutic efficacy in AD. The co-crystals of LZ and MTZ were synthesised and characterized using advanced analytical techniques, including Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Nuclear Magnetic Resonance (NMR) spectroscopy, confirming successful co-crystal formation. A topical cream was subsequently formulated and evaluated for its physicochemical properties, including pH, spreadability, viscosity, and in-vitro release study. The in vitro antimicrobial activity of the formulation was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans, pathogens frequently implicated in secondary infections in AD. Results demonstrated that the co-crystal significantly enhanced the solubility of LZ and exhibited enhanced antifungal and antibacterial effects. The topical cream showed favourable physicochemical attributes and superior antimicrobial activity, positioning it as a promising dual-therapy approach for managing fungal and bacterial infections associated with atopic dermatitis. This novel formulation addresses critical challenges in the treatment of AD, offering a potential improvement in clinical outcomes and patient compliance.

Graphical Abstract