Fluoxetine HCl-Loaded Nanostructured Lipid Carriers for Nose-to-Brain Delivery: Optimization and Synergistic Role of Saffron Oil

IF 2.7 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2025-09-29 DOI:10.1007/s12031-025-02411-x

Avinash R. Tekade, Prasad V. Kadam, Manoj K. Aswar, Anil B. Gaikwad, Rohit B. Shinde, Snehal S. Kharade

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引用次数: 0

Abstract

Objectives

Depression is a widespread psychiatric condition marked by ongoing sadness, disinterest, insomnia, and thoughts of self-harm. Fluoxetine HCl (FH) is a frequently prescribed antidepressant; however, it has low oral bioavailability (28%) due to significant first-pass metabolism and has side effects such as low blood pressure, gastrointestinal discomfort, and blurred vision. This research aimed to create and assess a novel intranasal nanostructured lipid carrier (NLC) system for FH, utilizing saffron oil (SO) as a functional lipid to enhance brain delivery while minimizing systemic side effects.

Methods

FH-NLCs were prepared using the high-pressure homogenization and ultrasonication method and was optimized based on particle size, PDI, Drug loading and entrapment efficiency.

Results

The observed mean particle size of FH-NLCs is 117.3 nm, PDI 0.219, and ZP -44.76 mV which were ideal for nose-to-brain delivery. The optimized formulation showed high drug loading and entrapment efficiency. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed a uniform morphology, while X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated partial amorphization of the drug within the lipid matrix. The in vitro drug release exhibited a sustained profile without burst release, adhering to Korsmeyer-Peppas kinetics, which showed non-fickian diffusion Super Case II Transport (n = 1.14). Ex vivo permeation studies on goat nasal mucosa revealed significantly enhanced nasal mucosal permeability compared to the FH solution, indicating the permeation-enhancing properties of SO. Histopathological assessments confirmed the formulation's safety for nasal application. The pharmacodynamic evaluations demonstrated a synergistic antidepressant effect between FH and SO, thereby supporting improved therapeutic efficacy.

Conclusion

The intranasal delivery of FH through SO-based NLCs offers a promising approach for direct brain targeting, potentially enhancing clinical outcomes in depression while reducing systemic side effects of FH.

查看原文本刊更多论文

氟西汀hcl负载的纳米结构脂质载体鼻至脑递送：优化和藏红花油的协同作用。

目的：抑郁症是一种普遍存在的精神疾病，其特征是持续的悲伤、冷漠、失眠和自残的想法。氟西汀（FH）是一种常用的抗抑郁药；然而，由于首过代谢显著，口服生物利用度较低（28%），并有低血压、胃肠道不适和视力模糊等副作用。本研究旨在创建和评估一种新型鼻内纳米结构脂质载体（NLC）系统，利用藏红花油（SO）作为功能性脂质来增强脑输送，同时最大限度地减少全身副作用。方法：采用高压均质超声法制备FH-NLCs，并根据粒径、PDI、载药量和包封效率进行优化。结果：FH-NLCs的平均粒径为117.3 nm， PDI为0.219，ZP为-44.76 mV，适合经鼻至脑输送。优化后的配方具有较高的载药量和包封效率。透射电子显微镜（TEM）和扫描电子显微镜（SEM）证实了均匀的形态，x射线衍射（XRD）和差示扫描量热法（DSC）表明药物在脂质基质内部分非晶化。体外释放表现为持续释放，无爆发释放，符合Korsmeyer-Peppas动力学，表现为非粘滞扩散超级转运（n = 1.14）。山羊鼻黏膜的体外渗透研究显示，与FH溶液相比，SO显著增强了鼻黏膜的渗透性，表明SO具有增强渗透性的特性。组织病理学评估证实了该制剂鼻用的安全性。药效学评估显示FH和SO之间具有协同抗抑郁作用，从而支持提高治疗效果。结论：通过基于so的NLCs鼻内给药FH为直接靶向大脑提供了一种有前景的方法，可能会提高抑郁症的临床结果，同时减少FH的全身副作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.