title: Poly(ethylene glycol)-block-poly(D,L-lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery.
abstract: In this study, angiopep with high transcytosis capacity and parenchymal accumulation was used as a novel ligand for the brain-targeting delivery of poly(ethylene glycol)-block-poly(D,L-lactide acid) (PEG-PLA) micelles. Angiopep-2 was synthesized by solid-phase peptide synthesis, and then conjugated with maleimide-PEG-PLA to form angiopep-PEG-PLA. The micelles composed of methoxy-PEG-PLA (mPEG-PLA) and angiopep-PEG-PLA was prepared by film-hydration method. Near-infrared fluorescence dye, DiR was loaded into micelles to evaluate the brain-targeting ability of micelles with or without angiopep modification by near-infrared fluorescence imaging in vivo and ex vivo. Significant near-infrared (NIR) fluorescent signal was detected in the brain after angiopep-anchored micelles administration and further confirmed by imaging the whole brain and brain slices, compared with that of the micelles without modification. ¹²⁵I-radiolabeled angiopep-PEG-PLA micelles after intravenous administration in mice showed high brain accumulation for up to 24 h. These results indicate that angiopep-modified PEG-PLA micelle is a promising brain-targeting nanocarrier for lipophilic drugs.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Meng
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Yingkai
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D008823:Micelles; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: C531860:Angiopep-2; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols