title: Altered plasma and brain disposition of isopropylidene shikimic acid liposome in rats and the brain protection in cerebral ischemia-reperfusion.
abstract: BACKGROUND
  Cerebral ischemia-reperfusion (I/R) injury is a secondary injury caused by oxidative stresses and inflammatory responses after recovery from cerebral ischemia. Brain protective drugs were used to reduce the injury. In order to improve the distribution in brain and enhance the brain-protective efficacy, some pharmaceutical technologies were used to achieve brain targeting delivery.
  
  
  OBJECTIVE
  To investigate the physiological disposition of ISA liposome, and provide references for the further study about high-efficacy brain-protective preparations for I/R injury.
  
  
  METHODS
  Comparative studies were carried out. The pharmacodynamics in t-MCAO model rats were studied first, and then the pharmacokinetics and brain distribution of the two preparations were determined.
  
  
  RESULTS
  At the same dose, the efficacy of ISA liposome was better (P < 0.05). The efficacy was dose dependent, with significant difference of 20 mg/kg (P < 0.01) and indistinctive difference of 10 mg/kg (P = 0.22), compared with vehicle-treated rats. The parameters, T(1/2β), MRT and AUC were different significantly between the two preparations. The enhancement of brain distribution for ISA in the liposome was obvious, with the maximum concentration 7.18 μg/g, while close to zero for the solution group.
  
  
  CONCLUSIONS
  ISA liposome could increase the distribution in brain and enhance the efficacy significantly. The results revealed that the liposomal DDS was potential as a novel strategy for the treatment of cerebral I/R injury. In addition, further targeted modification, such as PEG-modified liposomes, which possess a long circulating property in the bloodstream, would further improve the targeting delivery to the brain and lead to more significant efficacy.
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
authors.forename: Changhai
authors.initials: C
authors.lastname: Qu
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Longfei
authors.initials: L
authors.lastname: Lin
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Jingchen
authors.initials: J
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Xingbin
authors.initials: X
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004339:Drug Compounding; D006207:Half-Life; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D012765:Shikimic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: C479295:3,4-oxoisopropylideneshikimic acid; D004337:Drug Carriers; D008081:Liposomes; D018696:Neuroprotective Agents; D012765:Shikimic Acid