Kuo Yung-Chih, Kuo Chan-Ying
Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China.
Int J Pharm. 2008 Mar 3;351(1-2):271-81. doi: 10.1016/j.ijpharm.2007.09.020. Epub 2007 Sep 22.
Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.
抗逆转录病毒药物透过血脑屏障(BBB)对于获得性免疫缺陷综合征(AIDS)的治疗至关重要。本研究考察了暴露于电磁场(EMF)对沙奎那韦(SQV)透过血脑屏障通透性的影响。体外血脑屏障模型基于人脑微血管内皮细胞(HBMEC),并评估了转运系统接收室中SQV的浓度。聚氰基丙烯酸丁酯(PBCA)、甲基丙烯酸甲酯-磺丙基甲基丙烯酸酯(MMA-SPM)和固体脂质纳米粒(SLN)被用作递送系统的载体。随着可可脂含量增加,SLN的细胞毒性降低。5mV的强度适合用于对HBMEC的研究且无明显凋亡。方波产生的通透性高于正弦波和三角波。在暴露于EMF的情况下,载体对SQV透过HBMEC单层的通透性顺序为SLN>PBCA>MMA-SPM。此外,更高的频率、调幅(AM)的调制或幅度深度,或调频(FM)的调制或偏差会产生更高的通透性。此外,调幅波对通透性的增强作用比对调频波更显著。纳米颗粒PBCA、MMA-SPM和SLN与EMF暴露的组合对SQV透过血脑屏障的转运行为有强烈影响。这种组合将有利于AIDS和其他脑部相关疾病治疗的临床应用。