ArticleAAPS PharmSciTech2025
Enhanced Ocular Delivery of Itraconazole via a Self-Emulsifying Drug Delivery System: Improved Antifungal Activity and Cellular Uptake.
Article in AAPS PharmSciTech, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Corneal fungal infections are a leading cause of blindness worldwide; however, poor ocular drug absorption limits current topical antifungal treatments. Itraconazole (ICZ), a potent antifungal agent, exhibits low aqueous solubility and limited permeability. This study aimed to develop self-emulsifying drug delivery systems (SEDDS) to enhance the solubility, permeability, and ocular cell uptake of ICZ, providing a more effective topical therapy. ICZ solubility was evaluated in various vehicles (Tween 80, Tween 60, Span 20, coconut oil, and olive oil). Ten optimized SEDDS formulations were prepared, with particle sizes ranging from 514 to 1,384 nm (tenfold dilution). In vitro drug permeation was assessed using Franz diffusion cells with a parallel artificial membrane permeability assay. Cellular uptake was evaluated in ocular cell lines, and drug diffusion kinetics were analyzed using the Higuchi model. Formulation stability was assessed over a 6-month period. Formulation F1 achieved the highest permeation (96.71% ± 1.99%), followed by F3 (96.33% ± 3.24%) and F2 (80.98% ± 2.85%), whereas ICZ-PEG showed minimal permeation (11.55% ± 2.80%). The Higuchi model indicated diffusion-controlled transport. Cellular uptake was highest for F3, followed by F1 and F2, with approximately 50.3-, 38.6-, and 12.3-fold higher uptake than ICZ-PEG, respectively. All ICZ-SEDDS formulations remained stable for > 6 months. ICZ-SEDDS markedly improved the solubility, permeability, and ocular cell uptake of ICZ compared with ICZ-PEG. The superior performance of formulation F3 highlights the potential of SEDDS as an effective strategy for overcoming limitations in topical antifungal therapy for corneal fungal infections.
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