Ketoconazole (KZ) is a broad-spectrum imidazole antifungal agent, used in opportunistic systemic fungal infection treatment. Gastrointestinal absorption of this drug is variable and depends on the pH of the absorption site. The objective of the investigation was the development and characterization of (KZ) loaded lipid nanoformulations (KZ-LNFs) such as solid lipid nanoparticles (KZ-SLNs) and nanostructured lipid carriers (KZ-NLCs) that could improve oral bioavailability and enhance antifungal activity through oral delivery. KZ-LNFs were prepared using homogenization aided with the sonication method, using dynasan 116 as solid lipid and castor oil as liquid lipid. Prepared KZ-LNFs were evaluated for physicochemical characteristics and optimized. Optimized KZ-LNFs were further evaluated using X-ray diffractometry (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), stability, and freeze-drying. Furthermore, optimized KZ-LNFs were evaluated for in vitro antifungal efficacy against Candida albicans, and bioavailability studies were carried out in Wistar rats by single oral administration compared with KZ suspension as control formulation (KZ-CS). The optimized KZ-SLN formulation showed particle size and entrapment efficiency of 210.9 ± 3.4 nm and 84.8 ± 1.5 % compared to 167.8 ± 5.8 nm and 95.3 ± 2.0 % for optimized KZ-NLC formulation. XRD complemented and confirmed DSC results, KZ was well entrapped inside the core of carrier systems in a molecularly dispersed state. Furthermore, KZ-LNFs formulations exhibited a spherical shape in SEM. In vitro release studies demonstrated a sustained release profile for KZ from KZ-LNFs over a 24 h. After oral administration of the optimized KZ-containing SLN and NLC formulations, there were 2-folds, 2.4-folds, and 2-folds, 2.7-folds enhancements in C_max and AUC_0→∞, respectively compared with KZ-CS. Both NLC and SLN formulations were stable over three months at 4 °C and 25 °C and showed an enhanced antifungal activity. Overall, SLN and NLC formulations considered as alternative delivery vehicles for KZ oral administration in fungal infections treatment.

酮康唑（KZ）是一种广谱咪唑类抗真菌药，用于机会性全身性真菌感染的治疗。该药物在胃肠道的吸收是可变的，取决于吸收部位的pH。研究的目的是开发和表征（KZ）负载的脂质纳米制剂（KZ-LNFs），例如固体脂质纳米颗粒（KZ-SLNs）和纳米结构脂质载体（KZ-NLCs），它们可以改善口服生物利用度并增强抗真菌活性通过口服递送。KY-LNFs是在超声法辅助下均质化制备的，以dynasan 116作为固体脂质，蓖麻油作为液体脂质。评估制备的KZ-LNF的理化特性并进行优化。使用X射线衍射仪（XRD）进一步评估了优化的KZ-LNF，差示扫描量热法（DSC），扫描电子显微镜（SEM），稳定性和冷冻干燥。此外，对优化的KZ-LNF进行了评估在体外对白念珠菌具有抗真菌功效，并通过与KZ悬浮液作为对照制剂（KZ-CS）相比，单次口服Wistar大鼠进行了生物利用度研究。优化的KZ-SLN配方的粒径和包封效率为210.9±3.4 nm和84.8±1.5％，而优化的KZ-NLC配方的粒径为167.8±5.8 nm和95.3±2.0％。XRD补充并证实了DSC结果，KZ以分子分散状态很好地包裹在载体系统的核心内部。此外，KZ-LNFs制剂在SEM中呈球形。体外释放研究表明，KZ在24小时内从KZ-LNFs持续释放。与KZ-CS相比，口服优化的含KZ的SLN和NLC制剂口服后，C _max和AUC _0→∞分别提高了2倍，2.4倍和2倍，2.7倍。NLC和SLN制剂在4°C和25°C的三个月内均稳定，并显示出增强的抗真菌活性。总体而言，SLN和NLC制剂被认为是真菌感染治疗中KZ口服给药的替代递送载体。