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电响应纳米脂质体作为按需药物递送平台用于癫痫治疗。

The electro-responsive nanoliposome as an on-demand drug delivery platform for epilepsy treatment.

机构信息

Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.

Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.

出版信息

Int J Pharm. 2024 Oct 25;664:124610. doi: 10.1016/j.ijpharm.2024.124610. Epub 2024 Aug 20.

Abstract

Nano-based drug delivery systems are regarded as a promising tool for efficient epilepsy treatment and seizure medication with the least general side effects and socioeconomic challenges. In the current study, we have designed a smart nanoscale drug delivery platform and applied it in the kindling model of epilepsy that is triggered rapidly by epileptic discharges and releases anticonvulsant drugs in situ, such as carbamazepine (CBZ). The CBZ-loaded electroactive ferrocene nanoliposomes had an average diameter of 100.6 nm, a surface charge of -7.08 mV, and high drug encapsulation efficiency (85.4 %). A significant increase in liposome size was observed in response to direct current (50-500 μA) application. This liposome-based drug delivery system can release CBZ at a fast rate in response to both direct current and pulsatile electrical stimulation in vitro. The CBZ-liposome can release the anticonvulsant drug upon epileptiform activity in the kindled rat model and can decline electrographic and behavioral seizure activity in response to electrical stimulation of the hippocampus with an initially subconvulsive current. With satisfactory biosafety results, this "smart" nanocarrier has promising potential as an effective and safe drug delivery system to improve the therapeutic index of antiepileptic drugs.

摘要

基于纳米的药物输送系统被认为是一种有前途的工具,可用于高效治疗癫痫和癫痫发作药物,具有最小的一般副作用和社会经济挑战。在目前的研究中,我们设计了一种智能纳米药物输送平台,并将其应用于由癫痫放电快速引发的癫痫点燃模型中,该模型可原位释放抗惊厥药物,如卡马西平 (CBZ)。载有 CBZ 的电化学生铁纳米脂质体的平均直径为 100.6nm,表面电荷为-7.08mV,药物包封效率高(85.4%)。在直流电(50-500μA)应用下,观察到脂质体尺寸显著增加。这种基于脂质体的药物输送系统可以在体外对直流电和脉动电刺激快速释放 CBZ。CBZ-脂质体可以在点燃的大鼠模型中释放抗惊厥药物,并可以在海马区接受初始亚惊厥电流的电刺激时,降低脑电图和行为性癫痫发作活动。这种“智能”纳米载体具有良好的生物安全性,有望成为一种有效的、安全的药物输送系统,以提高抗癫痫药物的治疗指数。

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