title: A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice.
abstract: Due to the impermeability of the blood-brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood-brain barrier permeability-surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Tingting
authors.initials: T
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, People's Republic of China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, People's Republic of China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University.
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D000066829:Neuroprotection / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D056951:Photoelectron Spectroscopy; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution; D014168:Transferrin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D011108:Polymers; D014168:Transferrin; C075222:amyloid beta-protein (1-42); D003474:Curcumin
keywords: Alzheimer’s disease; Tet-1 peptide; polymersomes; transferrin