Enhancing therapeutic efficacy of fingolimod via intranasal delivery in an ethidium bromide-induced model of multiple sclerosis

IF 2.7 4区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Neuroscience Methods Pub Date : 2025-03-08 DOI:10.1016/j.jneumeth.2025.110415

Anshul Sharma , Nitin Sharma , Kushagra Khanna , Akshita Arora , Sidharth Mehan , Anjana Sharma

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引用次数: 0

Abstract

Background

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological characterized by muscle weakness, numbness, tingling, vision problems, and difficulty in coordination and balance caused by the damage of myelin content around the nerve fibres. The recent literature is evident that along with their lymphocyte attack prevention mechanism, fingolimod (FNG) can serve as neuroprotective also by ensuring their improved brain availability. Therefore, in this project brain availability of FNG was enhanced by delivering the FNG in the form of nanoparticles.

New methods

Fingolimod-loaded solid lipid nanoparticles (FNG-SLNs) were prepared using the solvent evaporation method and formulation factors (lipid concentration; X1, speed; X2, surfactant concentration; X3) and response were established by factorial design. FNG-SLNs were characterized for particle size, entrapment efficiency and in-vitro drug release. Optimized formulations were characterized for in-vivo efficacy study in ethidium bromide-induced MS rat model.

Result

Obtained data revealed that the particle size and entrapment efficiency of FNG-SLNs optimized formulation was 125.4 nm and 79.86 % w/w respectively. In-vitro drug release study showed an initial burst release of the FNG up to 32.52 % in 30 min followed by sustained drug release up to 78.22 % in 24 h. Furthermore, in-vivo data of FNG-SLNs on ethidium bromide-induced MS rat model revealed better treatment response by showing several evidence such as signs of remyelination, restoration of neuron shape, and the recovered oligodendrocytes.

Comparison with existing methods

To the best of our knowledge this article demonstrates improved efficacy of FNG using SLNs.

Conclusion

This study demonstrates the successful development of FNG-SLNs to enhance the therapeutic efficacy of FNG for the treatment of multiple sclerosis.

查看原文本刊更多论文

溴化乙啶诱导多发性硬化症模型鼻内给药提高芬哥莫德的治疗效果。

背景：多发性硬化症（MS）是一种慢性炎症性自身免疫性神经系统疾病，以肌肉无力、麻木、刺痛、视力问题、协调和平衡困难为特征，由神经纤维周围髓磷脂含量的损伤引起。最近的文献表明，随着它们的淋巴细胞攻击预防机制，fingolimod （FNG）也可以通过确保其改善的大脑可用性来起到神经保护作用。因此，在这个项目中，通过以纳米颗粒的形式输送FNG来增强FNG在大脑中的可用性。新方法：采用溶剂蒸发法制备负载fingolimod的固体脂质纳米颗粒（FNG-SLNs）。X1,速度;X2，表面活性剂浓度；X3)和响应通过析因设计建立。研究了fng - sln的粒径、包封效率和体外释药效果。对优化后的制剂进行了溴化乙锭诱导的MS大鼠体内药效研究。结果：所得数据显示，优化后的ng - slns粒径为125.4nm，包封效率为79.86% w/w。体外释药研究表明，FNG在30min内的初始爆发释放达到32.52%，24h内的持续释药达到78.22%。此外，在溴化乙锭诱导的MS大鼠模型上，fn - slns的体内数据显示出更好的治疗反应，如髓鞘再生迹象、神经元形状恢复、少突胶质细胞恢复等。与现有方法的比较：据我们所知，本文证明了使用sln的FNG的疗效有所提高。结论：本研究成功开发了FNG- slns，提高了FNG治疗多发性硬化症的疗效。

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 Neuroscience Methods 医学-神经科学

CiteScore

7.10

自引率

3.30%

发文量

226

审稿时长

52 days

期刊介绍： The Journal of Neuroscience Methods publishes papers that describe new methods that are specifically for neuroscience research conducted in invertebrates, vertebrates or in man. Major methodological improvements or important refinements of established neuroscience methods are also considered for publication. The Journal''s Scope includes all aspects of contemporary neuroscience research, including anatomical, behavioural, biochemical, cellular, computational, molecular, invasive and non-invasive imaging, optogenetic, and physiological research investigations.