Abstract：
Depression, the second biggest cause of disability worldwide, is widespread. Many antidepressant medications, including Desvenlafaxine Succinate (D.V.S.), function by elevating neurotransmitter levels at the synapse through the inhibition of reabsorption by neurons. However, the effectiveness of these treatments is often limited by their inability to reach the brain using conventional administration methods. Bilosome-stabilized nanovesicles containing bile salts have drawn much interest because of their adaptability and versatility in various applications. This study aimed to address this issue by formulating intranasal bilosomes incorporated into a mucoadhesive in situ gel to deliver D.V.S. directly to the brain for depression treatment. The desvenlafaxine-loaded bilosomes were developed using a thin film hydration method based on the l-optimal design. They were intended to provide a more convenient route of administration for antidepressants, enhancing bioavailability and brain targeting through intranasal delivery. The study assessed the optimized bilosomes for particle size (311.21 ± 0.42 nm), Zeta potential (-37.35 ± 0.43)and encapsulation efficiency (99.53 ± 0.41%) and further evaluated them in ex vivo and in vivo pharmacokinetics studies. Pharmacokinetic data reveal enhanced brain uptake compared to a free drug. A statistically optimized bilosome formulation was determined. The intranasal administration of mucoadhesive in situ gel containing desvenlafaxine succinate-loaded bilosomes facilitated direct nose-to-brain drug delivery, improving brain bioavailability.
摘要：
抑郁症,全球第二大残疾原因，是广泛的。许多抗抑郁药物，包括琥珀酸去文拉法辛（D.V.S.），通过抑制神经元的重吸收来提高突触的神经递质水平。然而,这些治疗的有效性通常受到使用常规给药方法无法到达大脑的限制。由于其在各种应用中的适应性和多功能性，含有胆汁盐的Bilosome稳定的纳米囊泡引起了极大的兴趣。本研究旨在通过配制掺入粘膜粘附原位凝胶以将D.V.S.直接递送至大脑用于抑郁症治疗的鼻内胆汁来解决这一问题。使用基于l-最优设计的薄膜水合方法开发了负载去文拉法辛的胆汁体。它们旨在为抗抑郁药提供更方便的给药途径，通过鼻内递送增强生物利用度和脑靶向性。该研究评估了优化的胆汁体的粒径（311.21±0.42nm），Zeta电位（-37.35±0.43）和包封效率（99.53±0.41％），并在离体和体内药代动力学研究中进一步评估。药代动力学数据显示与游离药物相比增强的脑摄取。确定了统计学上优化的Bilosome制剂。鼻内施用含有去文拉法辛琥珀酸盐负载的胆汁体的粘膜粘附原位凝胶促进了直接的鼻-脑药物递送，改善大脑生物利用度。
