Ahmed Osama A A, Fahmy Usama A, Badr-Eldin Shaimaa M, Aldawsari Hibah M, Awan Zuhier A, Asfour Hani Z, Kammoun Ahmed K, Caruso Giuseppe, Caraci Filippo, Alfarsi Anas, Al-Ghamdi Raniyah A, Al-Ghamdi Rawan A, Alhakamy Nabil A
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Nanomaterials (Basel). 2020 Jun 29;10(7):1270. doi: 10.3390/nano10071270.
Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box-Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.
氟立班丝氨（FLB）是一种经美国食品药品监督管理局（FDA）批准用于治疗女性性欲减退症的非激素类药物。然而，由于其广泛的首过效应和较差的溶解性，该药物的口服给药受到其低生物利用度的极大影响。为了克服这些缺点，本研究涉及制备优化的载有氟立班丝氨传递体（TRF）的鼻内水凝胶。采用Box-Behnken设计来改进尺寸减小的氟立班丝氨传递体。氟立班丝氨与磷脂的摩尔比、边缘活化剂的亲水亲油平衡以及水化介质的pH值均对传递体尺寸有显著影响。优化/开发的传递体呈单层形状。与对照载氟立班丝氨水凝胶相比，填充优化后的氟立班丝氨传递体的羟丙基甲基纤维素基水凝胶的体外渗透性能有所提高。此外，在Wistar大鼠鼻内给药后，优化的载传递体水凝胶相对于对照水凝胶表现出更高的生物利用度和增强的脑内递送。这些结果预示了所提出的载有优化的氟立班丝氨-传递体的鼻内水凝胶在提高药物生物利用度和鼻脑递送方面的潜在应用可能性。
