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载有琥珀酸舒马普坦的聚合物固体脂质纳米粒经鼻腔给药用于脑部靶向。

Intranasal drug delivery of sumatriptan succinate-loaded polymeric solid lipid nanoparticles for brain targeting.

机构信息

Formulation and Development of Injectable Department, Zydus Cadila Health Care Ltd, Ahmedabad, India.

Institute of Pharmaceutical Research (IPR), GLA University, Chaumuhan Mathura, India.

出版信息

Drug Dev Ind Pharm. 2022 Jan;48(1):21-28. doi: 10.1080/03639045.2022.2090575. Epub 2022 Jun 21.

Abstract

Migraine is a frequent neurological condition characterized by throbbing headaches, nausea, photophobia, and phonophobia, among other symptoms. Sumatriptan belongs to a BCS class III, which exhibits poor oral bioavailability and several side-effects. The objective of the present study was to develop solid lipid nanoparticles (SLNPs) of sumatriptan succinate for brain targeting by nasal route. Solvent injection method was used to increase the entrapment efficiency of hydrophilic drug. Thus, formulation was optimized by central composite design with minimum particle size, optimized zeta potential, and maximum entrapment efficiency, which was found to be 133.4 nm, -17.7 mV, and 75.5%, respectively. Optimized batch was further evaluated for surface morphology, Fourier-transform infrared spectroscopy, release, permeation across nasal mucosa, and histopathology. It was seen that most of the particles were spherical in shape as confirmed by scanning electron microscopy and transmission electron microscopy. The release of drug through the lipid showed initial burst release followed by sustained release up to 12 h. The diffusion study using goat nasal mucosa at pH 6.8 revealed that SLNPs permeation across nasal mucosa was quick, which was sufficient for brain targeting. Histopathology studies further revealed integrity of nasal mucosa after treatment with SLNPs. The investigation indicated that hydrophilic drug, sumatriptan succinate can be successfully entrapped in SLNPs to target brain nasal delivery, and thus it could be an effective approach for nose-to-brain delivery.

摘要

偏头痛是一种常见的神经系统疾病,其特征为搏动性头痛、恶心、畏光和恐声等症状。舒马曲坦属于 BCS 分类 III,其口服生物利用度差且有多种副作用。本研究的目的是通过鼻腔途径将琥珀酸舒马曲坦制成固体脂质纳米粒(SLNPs)以实现脑部靶向。溶剂注入法被用于提高亲水性药物的包封效率。因此,采用中心复合设计对制剂进行优化,以获得最小粒径、优化的 Zeta 电位和最大包封效率,分别为 133.4nm、-17.7mV 和 75.5%。优化后的批次进一步评估了表面形态、傅里叶变换红外光谱、释放、透过鼻黏膜的渗透和组织病理学。结果表明,大多数粒子呈球形,这一点通过扫描电子显微镜和透射电子显微镜得到了证实。药物通过脂质的释放显示出初始突释,随后持续释放至 12 小时。在 pH 6.8 的山羊鼻黏膜上进行的扩散研究表明,SLNPs 能够快速透过鼻黏膜进行脑靶向输送。组织病理学研究进一步表明,经 SLNPs 处理后鼻黏膜完整。该研究表明,亲水性药物琥珀酸舒马曲坦可以成功地包封在 SLNPs 中,用于脑靶向鼻腔给药,因此它可能是一种有效的鼻内递药方法。

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