title: The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.
abstract: Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, West Wenhua Road 107, Jinan 250012, P. R. China.
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Zhao
authors.forename: An-chang
authors.initials: AC
authors.lastname: Liu
authors.forename: Shu-wen
authors.initials: SW
authors.lastname: Yu
authors.forename: Zeng-xin
authors.initials: ZX
authors.lastname: Wang
authors.forename: Xiao-qian
authors.initials: XQ
authors.lastname: Lin
authors.forename: Guang-xi
authors.initials: GX
authors.lastname: Zhai
authors.forename: Qing-zhu
authors.initials: QZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D003487:Cyanoacrylates / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004659:Enbucrilate; D020244:Infarction, Middle Cerebral Artery; D007529:Isoflavones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D003487:Cyanoacrylates; D003911:Dextrans; D007529:Isoflavones; D018696:Neuroprotective Agents; C116176:PEO-PPO-PEO; D011136:Polysorbates; D011409:Propylene Glycols; D011092:Polyethylene Glycols; D004659:Enbucrilate; C033607:puerarin