title: In vitro and in vivo studies on gelatin-siloxane nanoparticles conjugated with SynB peptide to increase drug delivery to the brain.
abstract: BACKGROUND
  Nanobiotechnology can provide more efficient tools for diagnosis, targeted and personalized therapy, and increase the chances of brain tumor treatment being successful. Use of nanoparticles is a promising strategy for overcoming the blood-brain barrier and delivering drugs to the brain. Gelatin-siloxane (GS) nanoparticles modified with Tat peptide can enhance plasmid DNA transfection efficiency compared with a commercial reagent.
  
  
  METHODS
  SynB-PEG-GS nanoparticles are membrane-penetrable, and can cross the blood-brain barrier and deliver a drug to its target site in the brain. The efficiency of delivery was investigated in vivo and in vitro using brain capillary endothelial cells, a cocultured blood-brain barrier model, and a normal mouse model.
  
  
  RESULTS
  Our study demonstrated that both SynB-PEG-GS and PEG-GS nanoparticles had a spherical shape and an average diameter of 150-200 nm. It was shown by MTT assay that SynB-PEG-GS nanoparticles had good biocompatibility with brain capillary endothelial cells. Cellular uptake by SynB-PEG-GS nanoparticles was higher than that for PEG-GS nanoparticles for all incubation periods. The amount of SynB-PEG-GS nanoparticles crossing the cocultured blood-brain barrier model was significantly higher than that of PEG-GS nanoparticles at all time points measured (P < 0.05). In animal testing, SynB-PEG-GS nanoparticle levels in the brain were significantly higher than those of PEG-GS nanoparticles at all time points measured (P < 0.01). In contrast with localization in the brain, PEG-GS nanoparticle levels were significantly higher than those of SynB-PEG-GS nanoparticles (P < 0.01) in the liver.
  
  
  CONCLUSIONS
  This study indicates that SynB-PEG-GS nanoparticles have favorable properties with regard to morphology, size distribution, and toxicity. Moreover, the SynB-PEG-GS nanoparticles exhibited more efficient brain capillary endothelial cell uptake and improved crossing of the blood-brain barrier. Further, biodistribution studies of rhodamine-loaded nanoparticles demonstrated that modification with the SynB peptide could not only improve the ability of PEG-GS nanoparticles to evade capture in the reticuloendothelial system but also enhance their efficiency in crossing the blood-brain barrier.
authors.affiliation: Neurosurgical Department of Affiliated Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Tian
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Tian-xiao
authors.initials: TX
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xiao-ning
authors.initials: XN
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002199:Capillary Permeability; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D042783:Endothelial Cells / Q000378:metabolism; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley; D012833:Siloxanes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D010455:Peptides; D012833:Siloxanes; D011092:Polyethylene Glycols; D005780:Gelatin