title: Transport of saquinavir across human brain-microvascular endothelial cells by poly(lactide-co-glycolide) nanoparticles with surface poly-(γ-glutamic acid).
abstract: Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with surface poly-(γ-glutamic acid) (γ-PGA) were applied to enhance the transport of saquinavir (SQV) across the blood-brain barrier (BBB). PLGA NPs encapsulated SQV and grafted with γ-PGA to form drug carriers (γ-PGA/SQV-PLGA NPs) for crossing through a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated with human astrocytes. The results revealed that a lower molecular weight of γ-PGA yielded a higher grafting efficiency of γ-PGA on PLGA NPs. In addition, γ-PGA with a low molecular weight accelerated the dissolution of SQV from γ-PGA/SQV-PLGA NPs. A higher grafting efficiency (more didecyl dimethylammonium bromide) and a lower molecular weight of γ-PGA increased the permeability of SQV across the BBB, in general. When the grafting efficiency was 85.2% at 6kDa of γ-PGA, γ-PGA/SQV-PLGA NPs reached about 6 times the permeability of free SQV (the maximal permeability). γ-PGA could also promote the endocytosis of NPs and expression of ornithine decarboxylase by HBMECs. γ-PGA/SQV-PLGA NPs are efficacious nanoparticulate carriers in delivering antiretroviral drug across the BBB.
authors: Department of Chemical Engineering, National Chung Cheng University, Taiwan, Republic of China. chmyck@ccu.edu.tw
authors: Yung-Chih
authors: YC
authors: Kuo
authors: Hsin-Wei
authors: HW
authors: Yu
mesh_terms: D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000378:metabolism; D018920:Coculture Techniques; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry / Q000493:pharmacokinetics*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000493:pharmacokinetics; D019258:Saquinavir / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D011098:Polyglactin 910; D009955:Ornithine Decarboxylase; D019258:Saquinavir