Abstract: Transport of antiretroviral agents into the central nervous system is an important issue because human immunodeficiency viruses (HIV) have been found to reside and replicate themselves in the brain parenchyma. This yields a complicated treatment for the acquired immunodeficiency syndrome. Recently, novel nanoparticles (NPs) have been developed for carrying anti-HIV drugs across the blood-brain barrier (BBB). In this presentation, the anti-HIV drugs incorporated with NPs to circumvent the BBB included zidovudine, lamivudine, stavudine, didanosine, delavirdine, and saquinavir. These pharmaceuticals were loaded on the surfaces of polymeric NPs or entrapped in the matrix of solid lipid nanoparticles (SLNs). Polybutylcyanoacrylate, methylmethacrylate-co-sulfopropylmethacrylate, and poly(lactide-co-glycolide) were among the typical polymeric NPs, and various kinds of SLNs with lipid core of tripalmitin, cacao butter, docosanoic acid, stearic acid, and Compritol ATO 888 were also discussed. On the surfaces of the drug carriers, bioactive molecules including polysorbate 80, sorbitan monolaurate, phospatidylcholine, cholesteryl hemisuccinate, taurocholate, stearylamine, dioctadecyldimethyl ammonium bromide, heparin, L-arginine, and transferrin were applied to stabilization or modification. Effects of cold storage, pH value, synthesis duration, stirring speed, lyophilization, and composition on the drug delivery system, and physicochemical characteristics including particle size and shape, molecular weight, zeta potential, mobility, drug distribution, loading and entrapment efficiency, and release kinetics were shown. In addition, confluent monolayer of brain-microvascular endothelial cells (BMECs) from both bovine and human and an in vivo rat model were employed to the evaluation of permeability across the BBB. Presence of the medium chemicals including alcohol and glutamic acid was also considered. It was generally observed that cytotoxicity and transendothelial electrical resistance of BMECs cocultured with NPs were in reasonable range, and dramatic increase in the permeability of NPs-mediated system could be obtained. Moreover, impacts of the exposure to electromagnetic field (EMF) including power, wave type, frequency, modulation or depth of amplitude modulation, and modulation or deviation of frequency modulations were demonstrated. Finally, the evidence of vesicular endocytosis of drug-containing NPs by clathrin-coated endosome and the expression of tight junction and P-glycoprotein on the plasma membranes of BMECs were presented.

Brief Biography of the Speaker:
Dr. Yung-Chih Kuo is a professor at the Department of Chemical Engineering, National Chung Cheng University. His research interests are related to biomaterials, drug delivery system, tissue engineering, blood-brain barrier, nervous regeneration, cancer therapy, biophysics, and colloid and interface science. In these fields, he has authored or coauthored over 100 reviewed journal papers, abstracts, book chapters, and technical reports. He is an honor member of Phi Tau Phi Society and an active life member of Biochemical Engineering Society of Taiwan and Taiwan Institute of Chemical Engineers. He was often invited as a manuscript reviewer for over 20 journals and an external reviewer for academic awards, research grants, faculty recruitments and promotions, and hosting international symposium subsidy.