Sadiq Abubakar Hamza, Alam Md Jahangir, Begum Farhana, Hasan Mahedi, Kristof Jaroslav, Mamun Md Al, Maniruzzaman Md, Shimizu Kosuke, Kanazawa Takanori, Kahyo Tomoaki, Setou Mitsutoshi, Shimizu Kazuo
Graduate School of Science and Technology, Shizuoka University, Johoku, Chuo-ku, Hamamatsu 432-8561, Japan.
Graduate School of Medical Photonics, Shizuoka University, Johoku, Chuo-ku, Hamamatsu 432-8561, Japan.
Int J Mol Sci. 2025 Feb 17;26(4):1710. doi: 10.3390/ijms26041710.
Nose-to-brain (N2B) drug delivery is a promising technique for the treatment of brain diseases. It allows a drug to enter the brain without passing through the blood-brain barrier. However, the nasal cavity and nasal mucosa can restrict the amount of drug absorbed. Recent studies of non-thermal plasma (NTP) have shown improvement in in vitro drug delivery to cells and tissues. However, whether NTP treatments can enhance the in vivo delivery of drugs for neurodegenerative disease like Alzheimer's disease (AD) into the brain via the N2B technique remains unclear. The drug used in this study was galantamine hydrobromide. Galantamine is used to treat patients with mild to moderate AD. Based on the principle of NTP, a type of dielectric barrier discharge (DBD) plasma, which we called spiral DBD microplasma, was designed. It was inserted into the nose of a rat to a depth of 2 mm. The spiral DBD microplasma was driven by a sinusoidal voltage for 4 min, followed by the immediate administration of galantamine. The effect of the microplasma treatment on the distribution of galantamine in the brain was evaluated using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The results showed a high distribution of galantamine in the left and right brain hemispheres of the rat treated with plasma discharge compared to a control treated without plasma discharge. The spiral DBD microplasma is a novel contribution to DBD plasma designs. In addition, this technique for drug delivery has also created a novel approach with potential for becoming a non-invasive method of enhancing drug distribution in the brain for the treatment of neurological disorders.
鼻-脑(N2B)给药是一种治疗脑部疾病的很有前景的技术。它能使药物不通过血脑屏障而进入大脑。然而,鼻腔和鼻黏膜会限制药物的吸收量。最近关于非热等离子体(NTP)的研究表明,在体外向细胞和组织的药物递送方面有了改善。然而,NTP处理是否能通过N2B技术增强用于治疗神经退行性疾病如阿尔茨海默病(AD)的药物在体内向大脑的递送仍不清楚。本研究中使用的药物是氢溴酸加兰他敏。加兰他敏用于治疗轻度至中度AD患者。基于NTP原理,设计了一种介质阻挡放电(DBD)等离子体,我们称之为螺旋DBD微等离子体。将其插入大鼠鼻腔至2毫米深度。螺旋DBD微等离子体由正弦电压驱动4分钟,然后立即给予加兰他敏。使用基质辅助激光解吸/电离成像质谱(MALDI-IMS)评估微等离子体处理对加兰他敏在大脑中分布的影响。结果表明,与未进行等离子体放电处理的对照组相比,经等离子体放电处理的大鼠左右脑半球中加兰他敏的分布较高。螺旋DBD微等离子体是对DBD等离子体设计的一项新贡献。此外,这种药物递送技术还开创了一种新方法,有可能成为一种非侵入性方法,用于增强药物在大脑中的分布以治疗神经疾病。