title: Evaluation of Neuroprotective Effect of Thymoquinone Nanoformulation in the Rodent Cerebral Ischemia-Reperfusion Model.
abstract: The purpose of the present study was to evaluate the neuroprotective efficacy of optimized thymoquinone loaded PLGA-chitosan nanoparticles delivered via nose to brain route in the rodent cerebral ischemia-reperfusion model. The neuroprotective efficacy of the optimized thymoquinone loaded PLGA-chitosan nanoparticles was evaluated in middle cerebral artery occluded rats by various pharmacodynamic and biochemical studies. The pharmacokinetics of thymoquinone loaded PLGA-chitosan nanoparticles in the brain and blood plasma together with qualitative localization of florescent labelled PLGA-chitosan nanoparticles in brain tissues were also determined. Intranasal delivery of optimized thymoquinone loaded PLGA-chitosan nanoparticles (183.5 ± 8.2 nm, 33.63 ± 2.25 mV) to brain significantly reduced the ischemia infarct volume and enhanced the locomotor activity and grip strength in the middle cerebral artery occluded rats. Biochemical studies showed that intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles significantly reduced the lipid peroxidation but elevated the glutathione, catalase, and superoxide dismutase in the brain of middle cerebral artery occluded rats. The pharmacokinetic and localization studies showed that thymoquinone loaded PLGA-chitosan nanoparticles facilitated the delivery of thymoquinone to brain by intranasal nose to brain transport pathways and enhanced their pharmacokinetic profile in brain tissues. Thus, intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles to brain could be potentially used for the neuroprotection and treatment of cerebral ischemia.
authors.affiliation: Department of Anaesthesiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Xiao
authors.affiliation: Department of Anaesthesiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Ying-Xian
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Department of Gastrointestinal Surgery, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Ju-Yuan
authors.initials: JY
authors.lastname: Bu
authors.affiliation: Department of Spine Surgery, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Li
authors.affiliation: Department of Laboratory, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Zhou
authors.affiliation: Department of Anaesthesiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
authors.forename: Shao-Peng
authors.identifier: 0000-0001-7226-090X
authors.initials: SP
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; D018696:Neuroprotective Agents; C003466:thymoquinone