title: UEA I-bearing nanoparticles for brain delivery following intranasal administration.
abstract: Surface engineering of nanoparticles with lectins opened a novel pathway to improve the brain uptake of agents loaded by biodegradable PEG-PLA nanoparticles following intranasal administration. Ulex europeus agglutinin I (UEA I), specifically binding to l-fucose, which is largely located in the olfactory epithelium, was selected as a promising targeting ligand and conjugated onto the PEG-PLA nanoparticles surface with an optimized protocol relying on maleimide-mediated covalent binding technique. The in vivo results in rats suggested that UEA I modification at the nanoparticles surface facilitated the absorption of a fluorescent marker--6-coumarin associated with the nanoparticles into the brain following intranasal administration with significant increase in the area under the concentration-time curve (about 1.7 times) in different brain tissues compared with that of coumarin incorporated in the unmodified ones. UEA I-conjugation also elevated the brain-targeting efficiency of nanoparticles. Inhibition experiment of specific sugar suggested that the interactions between the nasal mucosa and the lectinised nanoparticles were due to the immobilization of carbohydrate-binding pockets on the surface of the nanoparticles. Distribution profiles of UEA I-modified nanoparticles indicated their higher affinity to the olfactory mucosa than to the respiratory one. Therefore, the UEA I-modified nanoparticles might serve as potential carriers for brain drug delivery, especially for mental therapeutics with multiple biological effects.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Weixing
authors.initials: W
authors.lastname: Tao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Chen
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005643:Fucose / Q000378:metabolism; D007096:Imidoesters / Q000737:chemistry; D007773:Lactates / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D053758:Nanoparticles; D009297:Nasal Mucosa / Q000378:metabolism*; D037121:Plant Lectins / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D003374:Coumarins; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007096:Imidoesters; D007773:Lactates; D008301:Maleimides; D037121:Plant Lectins; D013438:Sulfhydryl Compounds; C036850:Ulex europaeus lectins; C088513:poly(lactic acid-ethylene glycol); D005643:Fucose; D011092:Polyethylene Glycols; C005905:methyl 4-mercaptobutyrimidate