title: Transport of stavudine, delavirdine, and saquinavir across the blood-brain barrier by polybutylcyanoacrylate, methylmethacrylate-sulfopropylmethacrylate, and solid lipid nanoparticles.
abstract: Permeability of the anti-human immunodeficiency virus (HIV) agents, including stavudine (D4T), delavirdine (DLV), and saquinavir (SQV), across the in vitro blood-brain barrier (BBB) was studied. Here, the anti-HIV agents were incorporated with polybutylcyanoacrylate (PBCA) nanoparticles (NPs), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) NPs, and solid lipid nanoparticles (SLNs). Transport of the anti-HIV agents across BBB is a key factor in their applications to the therapy of the acquired immunodeficiency syndrome (AIDS). Experimental results revealed that the drug order of the loading efficiency (LE) on PBCA and MMA-SPM was D4T>DLV>SQV. For the entrapment efficiency (EE) in SLNs, this order was reversed. Also, LE of D4T on MMA-SPM was larger than that on PBCA; however, the reverse was true for DLV and SQV. As the particle size increased, LE decreased and EE increased. For a fixed drug carrier, an increase in the particle size yielded a decrease in the BBB permeability coefficient of the anti-HIV agents. Moreover, enhancement in the BBB permeability was on the carrier order of PBCA>MMA-SPM>SLNs for D4T, and for DLV and SQV, the order became PBCA>SLNs>MMA-SPM. PBCA, MMA-SPM, and SLNs were efficacious carriers of D4T, DLV, and SQV to meliorate BBB permeability by 3-16 folds, indicating the clinical potential of the present NP formulations for the AIDS treatment.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC. chmyck@ccu.ed.tw
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.forename: Fu-Lung
authors.initials: FL
authors.lastname: Su
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002199:Capillary Permeability; D002470:Cell Survival; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D020008:Delavirdine / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D004339:Drug Compounding; D017097:Electric Impedance; D004659:Enbucrilate / Q000737:chemistry*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008768:Methylmethacrylates / Q000737:chemistry*; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles; D019258:Saquinavir / Q000737:chemistry / Q000378:metabolism*; D018119:Stavudine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D008055:Lipids; D008768:Methylmethacrylates; D018119:Stavudine; D020008:Delavirdine; D004659:Enbucrilate; D019258:Saquinavir