Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Int J Nanomedicine. 2020 Jul 24;15:5253-5264. doi: 10.2147/IJN.S258791. eCollection 2020.
Flibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug's first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery.
Box-Behnken design was applied to explore the impact of solid lipid % (SL%, ), liquid lipid % (LL%, ), and sonication time (ST, ) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats.
Statistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3-6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs.
The aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.
氟班色林（FLB）是一种多功能血清素能药物，通过口服用于治疗绝经前妇女的低性欲障碍。据报道，FLB 的口服生物利用度有限，仅为 33%，这可能归因于药物的首过代谢。此外，FLB 的溶解度依赖于 pH 值，这可能是药物在体内中性液体中溶解的一个挑战因素，从而影响通过黏膜屏障的吸收。因此，本工作旨在研究利用纳米结构脂质载体（NLC）来克服上述缺点并增强鼻内递药的潜力。
采用 Box-Behnken 设计来探索固体脂质%（SL%， ）、液体脂质%（LL%， ）和超声时间（ST， ）对粒径的影响。对优化的 NLC 制剂进行了表征，并将其掺入到结冷胶原位凝胶中。对所制备的凝胶进行了体外药物释放、体内药代动力学性能和大鼠的组织病理学评估。
统计分析显示，SL%和 ST 对 NLCs 粒径均有显著的负影响，而 LL%则有显著的正影响。优化的制剂呈球形，囊泡大小为 114.63nm。与原始 FLB 控制凝胶相比，优化的 FLB-NLC 原位凝胶具有良好的稳定性和增强的体外释放。与原始 FLB 原位凝胶相比，大鼠鼻腔给药后药物的血浆和脑浓度分别增加了 3-6 倍以上。此外，组织病理学研究显示没有任何病理迹象。
上述结果突出了 FLB-NLC 鼻内原位凝胶的安全性及其提高药物生物利用度和脑内递药的潜力。
