title: Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery.
abstract: OBJECTIVE
  To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized.
  
  
  METHODS
  Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β(25-35) was investigated by immunohistochemical analysis.
  
  
  RESULTS
  The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls.
  
  
  CONCLUSIONS
  These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.
authors: Department of Pharmaceutics, School of Pharmacy, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Yuan
authors: Y
authors: Yu
authors: Zhiqing
authors: Z
authors: Pang
authors: Wei
authors: W
authors: Lu
authors: Qi
authors: Q
authors: Yin
authors: Huile
authors: H
authors: Gao
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D053148:Caspase 3 / Q000032:analysis; D003374:Coumarins / Q000032:analysis; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D007781:Lactoferrin / Q000737:chemistry / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013844:Thiazoles / Q000032:analysis; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D003374:Coumarins; D004337:Drug Carriers; C450880:Gly(14)-Humanin; D008081:Liposomes; D010455:Peptides; D013844:Thiazoles; C517282:coumarin 6; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D007781:Lactoferrin; D053148:Caspase 3