title: Intracellular delivery mechanism and brain delivery kinetics of biodegradable cationic bovine serum albumin-conjugated polymersomes.
abstract: BACKGROUND
  A novel brain drug delivery system using cationic bovine serum albumin (CBSA)-conjugated biodegradable polymersomes (CBSA-PO) was prepared, and its intracellular delivery mechanism and brain delivery kinetics were evaluated.
  
  
  RESULTS
  Biodegradable poly(ethylene glycol)-poly(ɛ-caprolactone) (PEG-PCL) was used to prepare the polymersomes, and thiolated CBSA was conjugated with the surface of the polymersome. Transmission electron microscopy and dynamic light scattering showed that the CBSA-PO had a round and vesicle-like shape, with a mean diameter of around 100 nm. Coupling of CBSA with polymersomes was confirmed by X-ray photoelectron spectroscopy. Uptake of CBSA-PO by bEnd.3 cells was significantly higher than that of unconjugated polymersomes, but was inhibited by low temperature, free CBSA, and poly-L-lysine, indicating that endocytosis was energy-driven and absorptive-mediated. Cell viability assays confirmed the good safety profile of biodegradable CBSA-PO. Pharmacokinetic results demonstrated that the polymersomes had long circulation times, and CBSA conjugation on the polymersomes significantly increased the blood-brain barrier permeability surface area product by 3.6-fold and the percentage of injected dose per gram brain (% ID/g brain) by 2.1-fold. Capillary depletion experiments showed that CBSA-PO was distributed into the brain parenchyma in a time-dependent manner, with few polymersomes detected, indicating that conjugation of polymersomes with CBSA significantly improved their transcytosis across the brain-blood barrier.
  
  
  CONCLUSIONS
  These results suggest that CBSA-PO is a promising drug brain delivery carrier with low toxicity.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai.
authors: Zhiqing
authors: Z
authors: Pang
authors: Huile
authors: H
authors: Gao
authors: Jun
authors: J
authors: Chen
authors: Shun
authors: S
authors: Shen
authors: Bo
authors: B
authors: Zhang
authors: Jinfeng
authors: J
authors: Ren
authors: Liangran
authors: L
authors: Guo
authors: Yong
authors: Y
authors: Qian
authors: Xinguo
authors: X
authors: Jiang
authors: Heng
authors: H
authors: Mei
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002417:Cattle; D002461:Cell Line, Transformed; D003374:Coumarins / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D005027:Ethylene Oxide / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D007700:Kinetics; D007783:Lactones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D013499:Surface Properties; D013816:Thermodynamics; D057900:Transcytosis
chemical_list: D003374:Coumarins; D004337:Drug Carriers; D007783:Lactones; C400421:PLC(20)-b-PEO(44); D012710:Serum Albumin, Bovine; D005027:Ethylene Oxide