Methylmethacrylate-sulfopropylmethacrylate nanoparticles with surface RMP-7 for targeting delivery of antiretroviral drugs across the blood-brain barrier.
This study investigates the capability of methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) nanoparticles (NPs) with grafted RMP-7 (RMP-7/MMA-SPM NPs) to deliver stavudine (D4T), delavirdine (DLV), and saquinavir (SQV) across the blood-brain barrier (BBB). The permeability coefficients of the three drugs across the BBB were evaluated by a co-culture model containing human brain-microvascular endothelial cells and human astrocytes. An increase in the concentration of ammonium persulfate (APS), the polymerization initiator, enhanced the particle size of drug-loaded RMP-7/MMA-SPM NPs. When the concentration of APS was 0.6%, the average particle diameter was smaller than 50 nm. These spherical drug carriers were uniform in size and displayed a dominant topography of discrete hillocks and deep pits in deposited film. Smaller RMP-7/MMA-SPM NPs yielded a larger drug loading efficiency. The order of drug in the loading efficiency and in the particle uptake was, respectively, D4T>DLV>SQV and D4T>SQV>DLV. Endocytosis of RMP-7/MMA-SPM NPs and tight junction mediation can improve the permeability of D4T, DLV, and SQV across the BBB.
Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, ROC. chmyck@ccu.edu.tw
Yung-Chih
YC
Kuo
Chin-Lung
CL
Lee
D000645:Ammonium Sulfate / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D020008:Delavirdine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D019258:Saquinavir / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018119:Stavudine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D019380:Anti-HIV Agents; D004337:Drug Carriers; D008689:Methacrylates; C089876:RMP 7; C031276:ammonium peroxydisulfate; D018119:Stavudine; D020008:Delavirdine; D019258:Saquinavir; D001920:Bradykinin; D000645:Ammonium Sulfate