title: Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG-TAT for drug delivery across the blood-brain barrier.
abstract: Biologically active polymer core/shell nanoparticles (i.e. micelles) self-assembled from TAT-poly(ethylene glycol) (PEG)-b-cholesterol (TAT-PEG-b-Chol) were fabricated and used as carrier for targeted blood-brain barrier delivery of antibiotics. Ciprofloxacin as a model antibiotic was efficiently loaded into the nanoparticles by a membrane dialysis method. The actual loading level of ciprofloxacin was dependent on initial loading of ciprofloxacin and fabrication temperature. The blank and ciprofloxacin-loaded nanoparticles were characterized using dynamic light scattering and SEM. The nanoparticles were spherical in nature, having an average size lower than 200 nm. The uptake of nanoparticles with TAT by human brain endothelial cells was greater than that of the nanoparticles without TAT. Most importantly, the nanoparticles with TAT were able to cross the blood-brain barrier (BBB), and located around the cell nucleus of neurons. These nanoparticles may provide a promising carrier to deliver antibiotics across the BBB for the treatment of brain infection.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.forename: Kian Chye
authors.initials: KC
authors.lastname: Ng
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Shabbir
authors.initials: S
authors.lastname: Moochhala
authors.forename: Yi-Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C490722:tat peptide (49-57), Human immunodeficiency virus 1; D011092:Polyethylene Glycols; D002784:Cholesterol