Ketoconazole-P Aminobenzoic Cocrystal Exhibits a Potent Anti-Inflammatory Effect on the Skin of BALB/c Mice

    Sorina Dănescu, Gabriela Adriana Filip, Remus Moldovan, Diana Olteanu, András Nagy, Xenia Filip, Flavia Martin, Irina Kacsó, Ioana Băldea
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    TLDR The new cocrystal KET-PABA is a more effective and safe anti-inflammatory treatment for skin conditions in mice.
    The document discusses a novel cocrystal formulation, KET-PABA, created from ketoconazole and para-amino benzoic acid, designed to enhance the bioavailability, biocompatibility, and efficiency of the parent drug. The cocrystal demonstrated improved stability, solubility, and antimycotic efficiency compared to ketoconazole. The study investigated the potential side effects of KET-PABA on the skin of BALBc mice, finding it to be safe with no signs of skin sensitization. Furthermore, KET-PABA exhibited a potent anti-inflammatory effect by inhibiting proinflammatory cytokines such as IL1α, IL1β, IL6, and TNFα, and other inflammation promoters like NRF2. It had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NFκB pathway. Therefore, KET-PABA cocrystal could potentially be an effective drug in treating cutaneous mycosis due to its improved antimycotic effect and anti-inflammatory action.
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