title: Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26.
abstract: A novel drug carrier for brain delivery, poly(ethyleneglycol)-poly(epsilon-caprolactone) (PEG-PCL) polymersomes conjugated with mouse-anti-rat monoclonal antibody OX26 (OX26-PO), was developed and its brain delivery property was evaluated. The diblock copolymers of methoxy-PEG-PCL and Maleimide-PEG-PCL were synthesized and applied to prepare polymersomes (PO) which were verified by direct cryogenic temperature transmission electron micrograph (Cryo-TEM) imaging. The TEM examination and dynamic light scattering results showed that OX26-PO had a round and vesicle-like shape with a mean diameter around 100 nm. Coupling of OX26 with PO was confirmed by immuno-gold labeling of OX26 visualized under the TEM and X-ray photoelectron spectroscopy test. The surface OX26 densities were obtained from enzyme-linked immunosorbant assay. The result of brain delivery in rats proved that the increase of surface OX26 density of OX26-PO decreased blood AUC. The optimized OX26 number conjugated per polymersome was 34, which can acquire the greatest blood-brain barrier (BBB) permeability surface area product and percentage of injected dose per gram brain (%ID/g brain). Furthermore, NC-1900, as a model peptide, was encapsulated into OX26(34)-PO and improved the scopolamine-induced learning and memory impairments in a water maze task via i.v. administration. These results indicated that OX26(34)-PO is a promising carrier for peptide brain delivery.
authors.affiliation: Department of Pharmaceutics, School of pharmacy, Fudan University, Shanghai 200032, PR China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Kaili
authors.initials: K
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Chaolin
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D019540:Area Under Curve; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D003374:Coumarins / Q000737:chemistry / Q000493:pharmacokinetics; D020285:Cryoelectron Microscopy; D004577:Electron Probe Microanalysis; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D016253:Microscopy, Immunoelectron; D053769:Nanocapsules / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000276:immunology; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D003374:Coumarins; D007783:Lactones; C115056:NC 1900; D053769:Nanocapsules; D009842:Oligopeptides; D011091:Polyesters; D011108:Polymers; D011990:Receptors, Transferrin; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D012601:Scopolamine; D011761:Pyrrolidonecarboxylic Acid