Hussain Afzal, Altamimi Mohammad A, Alneef Yaser Saleh
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Int J Pharm X. 2024 Aug 26;8:100279. doi: 10.1016/j.ijpx.2024.100279. eCollection 2024 Dec.
The study explored stearylamine containing cationic elastic liposomes to improve topical delivery and efficacy of ketoconazole (KETO) to treat deeply seated fungal infections. Stearylamine was used for dual functionalities (electrostatic interaction and flexibility in lipid bilayer). Hansen solubility program (HSPiP) estimated Hansen solubility parameters (HSP) based on the SMILE file and structural properties followed by experimental solubility study to validate the predicted values. Various formulations were developed by varying phosphatidylcholine and surfactants (tween 80 and span 80) concentration. To impart cationic properties, stearylamine (1.0 %) was added into the organic phase. Using quality by design (QbD) method, we optimized the formulations and evaluated for vesicle size, polydispersity index, zeta potential, morphology (scanning electron microscopy), in vitro drug release (%), and ex vivo permeation profiles. Result showed that there is a good correlation (0.65) between HSPiP predicted and actual experimental solubility of KETO in water, chloroform, S80, and tween 80. Spherical OKEL1 showed an established correlation between the predicted and the actual formulation parameters (size, zeta potential, and polydispersity index) (259 nm vs 270 nm, +2.4 vs 0.21 mV, and 0.24 vs 0.27). OKEL1 was associated with the highest value of %EE (83.1 %) as compared to liposomes. Finally, OKEL1 exhibited the highest % cumulative permeation (49.9 %) as compared to DS (13 %) and liposomes (25 %). Moreover, OKEL1 resulted in 4-fold increase in permeation flux as compared to DS which may be attributed to vesicular mediated improved permeation and gel based compensated trans epidermal water loss in the skin. The drug deposition elicited OKEL1 and OKEL1-gel as suitable carriers for maximum therapeutic benefit to treat deeply seated fungal infections.
该研究探索了含硬脂胺的阳离子弹性脂质体，以改善酮康唑（KETO）的局部递送及治疗深部真菌感染的疗效。硬脂胺具有双重功能（静电相互作用和脂质双层的柔韧性）。汉森溶解度程序（HSPiP）基于SMILE文件和结构特性估算汉森溶解度参数（HSP），随后进行实验溶解度研究以验证预测值。通过改变磷脂酰胆碱和表面活性剂（吐温80和司盘80）的浓度开发了各种制剂。为赋予阳离子特性，将硬脂胺（1.0%）添加到有机相中。采用质量源于设计（QbD）方法，我们优化了制剂，并对囊泡大小、多分散指数、zeta电位、形态（扫描电子显微镜）、体外药物释放（%）和离体渗透曲线进行了评估。结果表明，HSPiP预测的酮康唑在水、氯仿、司盘80和吐温80中的溶解度与实际实验溶解度之间存在良好的相关性（0.65）。球形OKEL1在预测和实际制剂参数（大小、zeta电位和多分散指数）之间显示出既定的相关性（259 nm对270 nm，+2.4对0.21 mV，以及0.24对0.27）。与脂质体相比，OKEL1的包封率（%EE）最高（83.1%）。最后，与二硬脂酰磷脂酰胆碱（DS，13%）和脂质体（25%）相比，OKEL1的累积渗透百分比最高（49.9%）。此外，与DS相比，OKEL1的渗透通量增加了4倍，这可能归因于囊泡介导的渗透改善以及凝胶对皮肤经表皮水分流失的补偿。药物沉积表明OKEL1和OKEL1-凝胶是用于治疗深部真菌感染以实现最大治疗益处的合适载体。
