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隐丹参酮纳米颗粒制剂的长期给药可减轻神经囊尾蚴病模型中的癫痫发作。

Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model.

作者信息

Mante Priscilla Kolibea, Adomako Nana Ofori, Antwi Paulina, Kusi-Boadum Nana Kofi

机构信息

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Department of Pharmacy Practice, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

出版信息

Curr Res Pharmacol Drug Discov. 2021 Jun 7;2:100040. doi: 10.1016/j.crphar.2021.100040. eCollection 2021.

Abstract

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model. A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 ​mg/kg), SLN-CRYP (5 ​mg/kg), ABZ (50 ​mg/kg) DXM (0.5 ​mg/kg), and PHE (30 ​mg/kg). were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains. All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p ​< ​0.0001); as were frequency (p ​< ​0.0001) and duration (p ​< ​0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p ​= ​0.0016) and IFN-γ (p ​< ​0.0001). Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

摘要

在全球范围内,神经囊尾蚴病仍然是后天性癫痫的一个重要病因。因此,我们试图研究隐丹参酮纳米颗粒制剂在神经囊尾蚴病模型中缓解癫痫发作的有效性。制备了提取的隐丹参酮的固体脂质纳米颗粒制剂。将寄生虫保存在感染了克氏假裸头绦虫(ORF株)的雌性BALB/c小鼠体内。对70只因感染克氏假裸头绦虫而出现癫痫发作的小鼠进行了隐丹参酮(5毫克/千克)、隐丹参酮固体脂质纳米粒(5毫克/千克)、阿苯达唑(50毫克/千克)、地塞米松(0.5毫克/千克)和苯妥英(30毫克/千克)的体外杀囊、体内杀囊和/或抗癫痫活性评估。研究了宿主组织中的一般病理过程,并从分离的小鼠大脑中对炎症介质进行了定量分析。所有治疗(隐丹参酮、隐丹参酮固体脂质纳米粒和阿苯达唑)均导致克氏假裸头绦虫囊肿的活力显著降低。在对脑进行检查时,隐丹参酮固体脂质纳米粒治疗显著缩小了囊尾蚴,并缓解了脑室扩张和移位,类似于阿苯达唑。隐丹参酮固体脂质纳米粒抑制了充血,但对小胶质细胞增生、钙化、水肿和脑膜炎更有效。在给予隐丹参酮固体脂质纳米粒的模型中,平均癫痫发作评分显著降低(p < 0.0001);癫痫发作的频率(p < 0.0001)和持续时间(p < 0.0001)也显著降低。隐丹参酮固体脂质纳米粒显著降低了脑匀浆中白细胞介素-10(p = 0.0016)和干扰素-γ(p < 0.0001)的水平。我们的研究表明,在小鼠模型中,长期给予隐丹参酮纳米颗粒制剂可有效缓解与神经囊尾蚴病相关的癫痫发作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d4b/8663984/cda1d20c41df/ga1.jpg

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