Flibanserin (FLB) is a multifunctional serotonergic agent that was recently approved by the FDA for the oral treatment of premenopausal women with hypoactive sexual desire disorder. FLB is a centrally acting drug that has a low oral bioavailability of 33% owing to its exposure to the hepatic first-pass effect, as well as its pH-dependent solubility, which could be an obstacle hindering the drug dissolution and absorption via mucosal barriers. Thus, this work aimed at overcoming the aforementioned drawbacks and promoting the nose-to-brain delivery of FLB via the formulation of an intra-nasal in situ niosomal gel. The Box–Behnken design was employed to study the impact of Span^® 85 concentration (X₁), hydration time (X₂), and pH of the hydrating buffer (X₃) on the vesicle size and drug entrapment. The optimized formulation exhibited a spherical shape with a vesicular size of 46.35 nm and entrapment efficiency of 92.48%. The optimized FLB niosomes integrated into gellan gum-based in situ gel exhibited enhanced ex vivo permeation and improved plasma and brain concentrations after nasal administration in rats compared to raw FLB. These findings highlight the capability of the proposed intra-nasal FLB niosomal in situ gel to boost the drug bioavailability and to promote its direct delivery to the brain.

中文翻译：

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鼻内囊泡原位凝胶作为增强氟班色林生物利用度和脑输送的有前途的方法：体外优化和离体/体内评估。


氟班色林 (FLB) 是一种多功能血清素药物，最近被 FDA 批准用于口服治疗患有性欲减退症的绝经前妇女。 FLB是一种中枢作用药物，由于其暴露于肝脏首过效应以及其pH依赖性溶解度，其口服生物利用度较低，为33%，这可能成为阻碍药物通过粘膜屏障溶解和吸收的障碍。因此，这项工作旨在克服上述缺点，并通过鼻内原位脂质体凝胶的配制促进FLB从鼻子到大脑的递送。采用 Box-Behnken 设计来研究 Span ^® 85 浓度 (X ₁ )、水合时间 (X ₂ ) 和水合缓冲液 pH 值 (X ₃ ) 对囊泡大小和药物包封的影响。优化后的制剂呈球形，囊泡尺寸为46.35 nm，包封率为92.48%。与原始 FLB 相比，整合到基于结冷胶的原位凝胶中的优化 FLB 囊泡在大鼠经鼻给药后表现出增强的离体渗透性以及改善的血浆和脑浓度。这些发现强调了所提出的鼻内 FLB 囊泡原位凝胶能够提高药物生物利用度并促进其直接递送至大脑的能力。