title: Expression of ornithine decarboxylase during the transport of saquinavir across the blood-brain barrier using composite polymeric nanocarriers under an electromagnetic field.
abstract: The expression of human ornithine decarboxylase (ODC) and permeability of saquinavir (SQV) across the blood-brain barrier were studied using nanoparticles (NPs) composed of poly(lactide-co-glycolide) (PLGA), poly-(γ-glutamic acid) (γ-PGA), and polyethyleneimine (PEI). SQV was encapsulated in the particle core to traverse a monolayer of human brain-microvascular endothelial cells (HBMECs) with the regulation of human astrocytes under an electromagnetic field (EMF). An increase in the weight percentage of PEI enhanced the particle size, zeta potential, and permeability of SQV. However, the viability of HBMECs reduced when the weight percentage of PEI increased. In addition, an increment in the molecular weight of γ-PGA enhanced the particle size and viability of HBMECs, and reduced the zeta potential. The permeability of SQV and expression of ODC were in the order: an EMF with amplitude modulation (AM)>an EMF with frequency modulation>no EMF. At 0.04% PEI, the AM EMF increased 2.38 times the uptake of NPs and 2.72 times the expression of ODC. The combination of PEI/γ-PGA/PLGA NPs and EMF can be an innovative strategy for delivering SQV into the brain.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC. chmyck@ccu.edu.tw
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Yu
mesh_terms: D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004574:Electromagnetic Fields; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D019258:Saquinavir / Q000378:metabolism*
chemical_list: D011108:Polymers; C511775:poly(gamma-glutamic acid); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011099:Polyglutamic Acid; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D009955:Ornithine Decarboxylase; D019258:Saquinavir