title: Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.
abstract: In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032,China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Weixing
authors.initials: W
authors.lastname: Tao
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Shoukuan
authors.initials: S
authors.lastname: Fu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism; D002923:Cilia / Q000187:drug effects; D004337:Drug Carriers / Q000493:pharmacokinetics*; D007096:Imidoesters / Q000737:chemistry; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D037102:Lectins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D049329:Nanostructures / Q000737:chemistry*; D009297:Nasal Mucosa / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D007096:Imidoesters; D037102:Lectins; D014909:Wheat Germ Agglutinins; C421282:poly(lactic acid)-poly(ethylene glycol)-monomethyl ether; D019344:Lactic Acid; D011092:Polyethylene Glycols; C005905:methyl 4-mercaptobutyrimidate