Ketoconazole (KZ) is broad spectrum antifungal drug, used for the treatment of fungal infections. KZ's clinical topical use has been associated with some adverse effects in healthy adults particularly local reactions, such as stinging, severe irritation, and pruritus. However, bioavailability of KZ after oral administration is low from tablets due to its low aqueous solubility. The objective of this investigation was development and characterization of KZ-containing solid lipid nanoparticles (KZ-SLNs) and SLN-containing hydrogel (KZ-SLN-H) for oral and topical delivery of KZ. KZ-SLNs were prepared using homogenization-sonication method. Optimal KZ-SLN formulation was selected based on physicochemical and in-vitro release studies. Optimized KZ-SLN converted to KZ-SLN hydrogel (KZ-SLN-H) using gelling polymers and optimized with rheological and in-vitro studies. Further, optimized KZ-SLN and KZ-SLN-H formulations evaluated for crystallinity, morphology, stability, ex-vivo and in-vivo pharmacokinetic (PK) studies in rats, comparison with KZ suspension (KZ-S) and KZ-S hydrogel (KZ-SH). Optimized KZ-SLN formulation showed desirable characters. KZ-SLN and KZ-SLN-H formulations exhibited spherical shape, converted to amorphous, sustained release behaviour and enhanced permeability (p < 0.05). Moreover, both formulations were stable for three months at 4 °C and 25 °C. PK studies revealed 1.9 and 1.5-folds, 3.5 and 2.8-folds enhancement of bioavailability of optimized KZ-SLN and KZ-SLN-H formulations (p < 0.05) compared with KZ-S and KZ-SH formulations, respectively. Overall, SLN and SLN-H formulations could be considered as an efficient delivery vehicles for KZ through oral and topical administration for better control over topical and systemic fungal infections.

酮康唑（KZ）是一种广谱抗真菌药，用于治疗真菌感染。KZ 的临床局部使用与健康成人的一些不良反应有关，特别是局部反应，如刺痛、严重刺激和瘙痒。然而，由于其水溶性低，口服给药后 KZ 的生物利用度从片剂中降低。本研究的目的是开发和表征含 KZ 的固体脂质纳米粒子 (KZ-SLN) 和含 SLN 的水凝胶 (KZ-SLN-H)，用于 KZ 的口服和局部递送。KZ-SLNs 是使用均质化-超声处理方法制备的。根据物理化学和体外释放研究选择最佳 KZ-SLN 配方。使用胶凝聚合物将优化的 KZ-SLN 转化为 KZ-SLN 水凝胶 (KZ-SLN-H)，并通过流变学和体外研究进行优化。此外，优化的 KZ-SLN 和 KZ-SLN-H 配方评估了结晶度、形态、稳定性、大鼠离体和体内药代动力学 (PK) 研究，与 KZ 悬浮液 (KZ-S) 和 KZ-S 水凝胶 (KZ-SH) 进行比较。优化的 KZ-SLN 配方显示出理想的特性。KZ-SLN 和 KZ-SLN-H 制剂表现出球形、转化为无定形、持续释放行为和增强的渗透性 (p < 0.05)。此外，这两种制剂在 4°C 和 25°C 下可稳定保存三个月。PK 研究显示，与 KZ-S 和 KZ-SH 制剂相比，优化的 KZ-SLN 和 KZ-SLN-H 制剂的生物利用度分别提高了 1.9 和 1.5 倍、3.5 和 2.8 倍（p < 0.05）。总体而言，SLN 和 SLN-H 制剂可被视为通过口服和局部给药的 KZ 有效递送载体，以更好地控制局部和全身真菌感染。