title: Preparation of Angiopep-2 Peptide-Modified Bubble Liposomes for Delivery to the Brain.
abstract: In the development of therapeutic approaches for central nervous system diseases, a significant obstacle is efficient drug delivery across the blood-brain barrier owing to its low permeability. Various nanocarriers have been developed for brain-targeted drug delivery by modification with specific ligands. We have previously developed polyethylene glycol-modified liposomes (Bubble liposomes [BLs]) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA or small interfering RNA carriers and US contrast agents. In this study, we attempted to prepare brain-targeting BLs modified with Angiopep-2 (Ang2) peptide (Ang2-BLs). Ang2 is expected to be a useful ligand for the efficient delivery of nanocarriers to the brain. We showed that Ang2-BLs interacted specifically with brain endothelial cells via low-density lipoprotein receptor-related protein-1. We also confirmed that Ang2-BLs could entrap US contrast gas and had US imaging ability as well as unmodified BLs. Furthermore, we demonstrated that Ang2-BLs accumulated in brain tissue after intravascular injection. These results suggested that Ang2-BLs may be a useful tool for brain-targeted delivery and US imaging via systemic administration.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo-Takahashi
authors.forename: Kotomi
authors.initials: K
authors.lastname: Ooaku
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ishida
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003287:Contrast Media / Q000008:administration & dosage; D042783:Endothelial Cells / Q000378:metabolism; D005466:Fluorocarbons / Q000008:administration & dosage; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D014463:Ultrasonography
chemical_list: C531860:Angiopep-2; D003287:Contrast Media; D005466:Fluorocarbons; D008055:Lipids; D008081:Liposomes; D010455:Peptides; D011092:Polyethylene Glycols; C042852:perflutren