Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Int J Nanomedicine. 2020 Jul 16;15:5113-5129. doi: 10.2147/IJN.S261855. eCollection 2020.
Low bioavailability and poor permeability of the blood-brain barrier are problematic when delivering therapeutic agents and particularly anti-human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery. Cubosomes have been reported as helpful vehicles for intranasal delivery of therapeutics to enable brain targeting.
In this study, we aimed to develop the intranasal cubosomal thermogelling dispersion of saquinavir mesylate for central nervous system delivery.
The Box-Behnken design was applied to study the effect of monoolein, Poloxamer 407, and polyvinyl alcohol as independent factors and the particle size, entrapment efficiency, gelation temperature, and stability index as responses. The optimized cubosomes were evaluated using transmission electron microscopy, ex vivo permeation, and in vivo pharmacokinetics.
The optimized formula consisting of monoolein (8.96%), Poloxamer 407 (17.45%), and polyvinyl alcohol (7.5%) was prepared and evaluated. Higher values for the steady-state flux, permeability coefficient, and enhancement factor were observed for the cubosomal thermogelling dispersion of saquinavir during ex vivo permeation in comparison with an aqueous suspension of saquinavir. From the pharmacokinetic profile, the relative bioavailability for the intranasal optimized formula was approximately 12-fold higher when compared with oral aqueous suspension and 2.5-fold greater when compared to the intranasal aqueous suspension of saquinavir.
Overall, the saquinavir-loaded cubosomal thermogelling formulation is promising for central nervous system delivery by intranasal administration.
将治疗药物，特别是抗人类免疫缺陷病毒治疗药物递送到中枢神经系统时，低生物利用度和血脑屏障通透性差是一个问题。鼻内途径为中枢神经系统递药提供了一种替代途径。 Cubosomes 已被报道为有助于将治疗剂经鼻内递送到大脑的载体。
本研究旨在开发硫酸茚地那韦 Cubosomes 鼻用温敏凝胶递药系统，用于中枢神经系统递药。
采用 Box-Behnken 设计研究单油酸甘油酯、泊洛沙姆 407 和聚乙烯醇作为独立因素，以及粒径、包封效率、胶凝温度和稳定性指数作为响应，对 Cubosomes 的进行研究。采用透射电子显微镜、离体渗透和体内药代动力学对优化的 Cubosomes 进行评价。
制备并评价了由单油酸甘油酯（8.96%）、泊洛沙姆 407（17.45%）和聚乙烯醇（7.5%）组成的优化配方。与硫酸茚地那韦的水性混悬剂相比，硫酸茚地那韦 Cubosomes 温敏凝胶递药系统在离体渗透过程中表现出更高的稳态通量、渗透系数和增强因子。从药代动力学特征来看，与口服水性混悬剂相比，鼻内优化配方的相对生物利用度约提高了 12 倍，与鼻内硫酸茚地那韦水性混悬剂相比，提高了 2.5 倍。
总之，载有硫酸茚地那韦的 Cubosomes 温敏凝胶制剂有望通过鼻内给药用于中枢神经系统递药。
