title: Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. chmyck@ccu.edu.tw
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.forename: Chan-Ying
authors.initials: CY
authors.lastname: Kuo
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D017209:Apoptosis; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002099:Cacao / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004574:Electromagnetic Fields; D004659:Enbucrilate / Q000737:chemistry; D042783:Endothelial Cells / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008689:Methacrylates / Q000737:chemistry; D053758:Nanoparticles; D010539:Permeability; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D008689:Methacrylates; D004659:Enbucrilate; D019258:Saquinavir