title: Brain delivery and cellular internalization mechanisms for transferrin conjugated biodegradable polymersomes.
abstract: Transferrin conjugated biodegradable polymersomes (Tf-PO) were exploited for efficient brain drug delivery, and its cellular internalization mechanisms were investigated. Tf-PO was prepared by a nanoprecipitation method with an average diameter of approximately 100 nm and a surface Tf molecule number per polymersome of approximately 35. It was demonstrated that the uptake of Tf-PO by bEnd.3 was mainly through a clathrin mediated energy-dependent endocytosis. Both the Golgi apparatus and lysosomes are involved in intracellular transport of Tf-PO. Thirty minutes after a 50mg/kg dose of Tf-PO or PO was injected into rats via the tail vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of Tf-PO than PO in the cerebral cortex, the periventricular region of the lateral ventricle and the third ventricle. The brain delivery results proved that the blood-brain barrier (BBB) permeability surface area product (PS) and the percentage of injected dose per gram of brain (%ID/g brain) for Tf-PO were increased to 2.8-fold and 2.3-fold, respectively, as compared with those for PO. These results indicate that Tf-PO is a promising brain delivery carrier.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ren
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wen
authors.forename: Jinghan
authors.initials: J
authors.lastname: Su
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014168:Transferrin / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011091:Polyesters; D014168:Transferrin; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols