WHEN A POTENT ANTIFUNGAL FALLS SHORT: RETHINKING ITRACONAZOLE BIOAVAILABILITY THROUGH NANOCARRIER-BASED DRUG DELIVERY

Successful pharmacotherapy depends not only on the pharmacological potency of a drug but also on its ability to reach adequate systemic concentrations within the body. In clinical practice, several therapeutically effective drugs face significant formulation challenges that limit their clinical performance. Itraconazole, a broad-spectrum triazole antifungal agent widely used for the treatment of systemic and superficial fungal infections, represents a notable example of such a limitation. Itraconazole is commonly prescribed in the management of infections including aspergillosis, histoplasmosis, candidiasis, and dermatophytosis. Despite its strong antifungal activity, itraconazole exhibits extremely poor aqueous solubility. According to the Biopharmaceutics Classification System (BCS), itraconazole is categorized as a Class II drug, characterized by low solubility but relatively high membrane permeability. Because of this property, dissolution in gastrointestinal fluids becomes the rate-limiting step for drug absorption. Consequently, variations in gastric pH, food intake, and gastrointestinal physiology can significantly influence drug absorption, sometimes resulting in inconsistent plasma concentrations and variable therapeutic responses among patients. Advances in pharmaceutical nanotechnology have introduced promising strategies to address these formulation challenges. Nanocarrier-based drug delivery systems such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, and nanoemulsions have demonstrated significant potential in enhancing the dissolution and systemic availability of poorly soluble drugs. Improving the delivery of poorly soluble drugs remains a major focus of modern pharmaceutical research. Nanocarrier-based strategies therefore represent a promising approach for optimizing itraconazole therapy and achieving more consistent therapeutic outcomes in the management of fungal infections. Keywords: Itraconazole, Nanocarriers, Bioavailability Enhancement, Antifungal Drug Delivery, Pharmaceutical Nanotechnology.