Mannosylated fisetin/carveol lipid nanocapsules: brain-targeted dual therapy for modulation of epileptogenesis and cognitive deficits.

IF 5.5 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-08-09 DOI:10.1007/s13346-025-01937-2

Julie R Youssef, Nabila A Boraie, Fatma A Ismail, Basant A Bakr, Eman A Allam, Mahmoud A Agami, Riham M El-Moslemany

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引用次数: 0

Abstract

Pharmacological treatment of epilepsy is challenged by several barriers with the blood brain barrier (BBB) imposing the utmost restrictions to brain drug delivery. Antiepileptic drugs aim to reduce seizures frequency and severity while exerting minimal toxic effects. Herein, the merits of phytomedicine and brain targeted nanocarriers were combined for the control of seizures in a chronic epilepsy model. Fisetin (FS); a polyphenol and carveol (CAR); a limonene monoterpenoid were selected for their neuroprotective roles and co-loaded into lipid nanocapsules (FS/CAR@LNC). This was further decorated with mannose by post insertion targeting glucose transporter (GLUT-1) overexpressed on BBB (MAN-FS/CAR@LNC). The optimized MAN-FS/CAR@LNC revealed good colloidal properties with particle size (53.17 ± 4.06 nm), and low polydispersity index (0.11) and 26.9 ± 1.05 mV zeta potential. A high entrapment efficiency exceeding 99% and sustained drug release profile over 72 h were observed for both FS and CAR. In the in vivo imaging system (IVIS), MAN-FS/CAR@LNC attained 1.3-fold increase in fluorescence intensity at 5 h interval compared to FS/CAR@LNC. Following intraperitoneal administration in PTZ- induced chronic epilepsy mouse model, MAN-FS/CAR@LNC achieved maximal control of epileptic seizures accompanied with rehabilitation of locomotion, depressive and anxiety like-behaviors compared to FS/CAR and FS/CAR@LNC. Similarly, analysis of biomarkers reflecting depression and anxiety actions (brain-derived neurotrophic factor; BDNF, serotonin and glutamate) together with inflammatory markers (IL-6 and IL-1ꞵ) and histopathological assessment affirmed MAN-FS/CAR@LNC excelling in enhancing LNC brain targetability and hence seizures control. In conclusion, FS/CAR co-therapy aided with mannosylated LNC could present a compelling podium for the effective management of CNS disorders.

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甘露糖基化非瑟酮/卡维罗脂质纳米胶囊：脑靶向双重疗法调节癫痫发生和认知缺陷。

癫痫的药物治疗受到几个障碍的挑战，其中血脑屏障（BBB）对脑药物输送施加了最大的限制。抗癫痫药物的目的是减少癫痫发作的频率和严重程度，同时发挥最小的毒性作用。本文将植物药物和脑靶向纳米载体的优点结合起来控制慢性癫痫模型中的癫痫发作。非瑟酮(FS);多酚和卡维罗（CAR）；选择具有神经保护作用的柠檬烯单萜类化合物，并将其共同装入脂质纳米胶囊（FS/CAR@LNC）。通过插入后靶向血脑屏障上过表达的葡萄糖转运蛋白（GLUT-1），进一步用甘露糖修饰（MAN-FS/CAR@LNC）。优化后的MAN-FS/CAR@LNC具有良好的胶体性能，粒径为53.17±4.06 nm，多分散性指数为0.11，zeta电位为26.9±1.05 mV。FS和CAR均具有超过99%的高包封效率和超过72 h的药物持续释放曲线。在体内成像系统（IVIS）中，MAN-FS/CAR@LNC与FS/CAR@LNC相比，间隔5 h的荧光强度增加了1.3倍。在PTZ诱导的慢性癫痫小鼠模型中，与FS/CAR和FS/CAR@LNC相比，MAN-FS/CAR@LNC在最大程度上控制了癫痫发作，并伴有运动、抑郁和焦虑样行为的康复。同样，分析反映抑郁和焦虑行为的生物标志物(脑源性神经营养因子；BDNF、血清素和谷氨酸)、炎症标志物（IL-6和IL-1ꞵ）和组织病理学评估证实了MAN-FS/CAR@LNC在增强LNC脑靶向性从而控制癫痫发作方面表现出色。综上所述，FS/CAR联合治疗与甘露糖化LNC可以为有效治疗中枢神经系统疾病提供一个令人信服的平台。

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

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.