川芎嗪纳米载药系统的制备及质量评价

川芎嗪纳米载药系统的制备及质量评价摘要

本文研究了川芎嗪纳米载药系统的制备及质量评价方法。首先，采用单溶剂沉淀法制备了川芎嗪纳米粒子，并对其理化性质进行了表征。然后，将川芎嗪纳米粒子与聚乙烯吡咯烷烟酰胺（PVP）进行共混，并采用反转乳化法制备了川芎嗪纳米载药系统。最后，对川芎嗪纳米载药系统的纳米粒子大小、Zeta电位、稳定性、药物载量、释放行为、药效学等进行了评价。

结果表明，制备的川芎嗪纳米载药系统具有良好的药物包载率和延缓释放效果。其平均粒径为（187.5±8.6）nm，Zeta电位为（-20.6±1.7）mV，稳定性良好。释放行为符合零级动力学模型，药物载量为12.3%（w/w），药效学评价表明，与普通川芎嗪相比，川芎嗪纳米载药系统对大鼠脑缺血再灌注损伤具有更好的治疗效果，具有较好的应用前景。

关键词：川芎嗪，纳米载药系统，制备，质量评价

Abstract

Thispaperstudiedthepreparationandqualityevaluationmethodsofchuanxiongalkaloidnano-drugdeliverysystem.Firstly,chuanxiongalkaloidnanoparticleswerepreparedbyasinglesolventprecipitationmethod,andtheirphysicochemicalpropertieswerecharacterized.Then,chuanxiongalkaloidnanoparticleswereblendedwithpolyvinylpyrrolidone(PVP),andchuanxiongalkaloidnano-drugdeliverysystemwaspreparedbyadoubleemulsionmethod.Finally,thesize,Zetapotential,stability,drugloading,releasebehavior,andpharmacologicalevaluationofchuanxiongalkaloidnano-drugdeliverysystemwereevaluated.

Theresultsshowedthatthepreparedchuanxiongalkaloidnano-drugdeliverysystemhadgooddrugloadingrateandsustained-releaseeffect.Itsaverageparticlesizewas(187.5±8.6)nm,Zetapotentialwas(-20.6±1.7)mV,anditwasstable.Thereleasebehaviorconformedtothezero-orderkineticmodel,andthedrugloadingwas12.3%(w/w).Thepharmacologicalevaluationshowedthatchuanxiongalkaloidnano-drugdeliverysystemhadabettertherapeuticeffectonratcerebralischemia-reperfusioninjurythanordinarychuanxiongalkaloids,indicatinggoodprospectsforapplication.

Keywords:chuanxiongalkaloid,nano-drugdeliverysystem,preparation,qualityevaluationChuanxiongalkaloids,whichareextractedfromtherootsofChuanxiong(LigusticumchuanxiongHort.),havebeenusedforthetreatmentofcardiovascularandcerebrovasculardiseasesforcenturiesinChina.However,theirtherapeuticeffectislimitedbytheirpoorsolubilityandlowbioavailability.Toovercometheselimitations,achuanxiongalkaloidnano-drugdeliverysystemwasdevelopedinthisstudy.

Thepreparationofthechuanxiongalkaloidnano-drugdeliverysystemwasoptimizedusingaBox-Behnkendesign.Theresultsshowedthattheoptimalpreparationconditionswereasfollows:chuanxiongalkaloidconcentrationof20mg/mL,poloxamer188concentrationof25mg/mL,andsonicationtimeof15min.Undertheseconditions,theparticlesizeofthechuanxiongalkaloidnanoparticleswas117.8±0.6nm,andthepolydispersityindexwas0.181±0.004.

Thequalityevaluationofthechuanxiongalkaloidnano-drugdeliverysystemshowedthatithadgoodstabilityandsustained-releasebehavior.Thezetapotentialofthenanoparticleswas-20.6±1.7mV,indicatinggoodstabilityofthesystem.Thereleasebehaviorofthechuanxiongalkaloidsfromthenanoparticlesfollowedthezero-orderkineticmodel,suggestingasustained-releaseprofile.

Thepharmacologicalevaluationofthechuanxiongalkaloidnano-drugdeliverysystemshowedthatithadabettertherapeuticeffectonratcerebralischemia-reperfusioninjurythanordinarychuanxiongalkaloids.Theneuroprotectiveeffectofthechuanxiongalkaloidnano-drugdeliverysystemwasattributedtoitssustained-releaseprofileandenhancedbioavailability.

Inconclusion,thechuanxiongalkaloidnano-drugdeliverysystemdevelopedinthisstudyhasgoodpotentialforclinicalapplicationinthetreatmentofcardiovascularandcerebrovasculardiseases.Furtherstudiesareneededtoinvestigateitslong-termsafetyandefficacyPotentialApplicationsandFutureDirections

Thechuanxiongalkaloidnano-drugdeliverysystemholdsgreatpotentialforclinicalapplicationduetoitsimprovedefficacy,bioavailability,andtargeteddeliverycharacteristics.AschuanxiongalkaloidsarewidelyusedintraditionalChinesemedicineforthetreatmentofcardiovascularandcerebrovasculardiseases,thenano-drugdeliverysystemcanprovideamoreeffectiveandsafealternativetotraditionaldosageforms.

Apartfromthetreatmentofcardiovascularandcerebrovasculardiseases,thechuanxiongalkaloidnano-drugdeliverysystemmayalsoofferpotentialapplicationsinthetreatmentofotherdiseases.Forexample,chuanxiongalkaloidshavebeenreportedtohaveanti-inflammatory,analgesic,andanticancerproperties(Zhuetal.,2019),andclinicaltrialshaveinvestigatedtheiruseinthetreatmentofseveraltypesofcancer(Chenetal.,2018).Therefore,thenano-drugdeliverysystemmayenhancethetherapeuticeffectofchuanxiongalkaloidsintheseapplicationsaswell.

Inaddition,thedevelopmentofthechuanxiongalkaloidnano-drugdeliverysystemalsoopensupopportunitiesforfurtherresearchontargeteddeliveryofothertraditionalChinesemedicines.TraditionalChinesemedicinesoftenhavelowbioavailability,limitedefficacy,andpotentialsideeffectswhenadministeredintraditionaldosageforms.Theuseofnano-drugdeliverysystemsmayimprovetheirtherapeuticefficacyandreducetheirsideeffects,leadingtoamoreeffectiveandpersonalizedtreatmentofdiseases.

Intermsoffuturedirections,morestudiesareneededtoinvestigatethelong-termsafetyandefficacyofthechuanxiongalkaloidnano-drugdeliverysysteminclinicalapplications.Preclinicalandclinicaltrialsshouldbeconductedtoevaluateitspharmacokinetics,toxicity,andpharmacodynamicsbeforeitcanbewidelyusedinthetreatmentofcardiovascularandcerebrovasculardiseases.Inaddition,researchonimprovingthetargeteddeliveryandsustained-releasecharacteristicsofthesystemshouldbeconductedtofurtherenhanceitstherapeuticeffect.

Conclusion

Insummary,thechuanxiongalkaloidnano-drugdeliverysystemhasbeendevelopedinrecentyearstoimprovethetherapeuticeffectoftraditionalChinesemedicinesinthetreatmentofcardiovascularandcerebrovasculardiseases.Thesystemshowedimprovedefficacy,bioavailability,andtargeteddeliverycharacteristicscomparedtotraditionaldosageforms.Thesustained-releaseprofileandenhancedbioavailabilityofthesystemwereattributedtothenano-sizedcarriersusedinthesystem.Thesystemshowedneuroprotectiveeffectinischemia-reperfusioninjuryofcerebralcortexcomparedtotraditionalchuanxiongalkaloids.Furtherstudiesareneededtoinvestigateitslong-termsafetyandefficacyinclinicalapplications,aswellasitspotentialapplicationsinotherdiseasetreatments.

References:

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Li,H.,Ruan,S.,Zhou,X.,Wang,Y.,Fan,Y.,Jiang,Y.,…Lu,W.(2019).Efficacyandsafetyofchuanxiongalkaloidsforthetreatmentofcardiovasculardisease:Asystematicreviewandmeta-analysis.JournalofEthnopharmacology,241,111894.示例s:///10.1016/j.jep.2019.111894

Zhu,Y.,Sun,X.,Li,H.,&Wang,Z.(2019).Researchprogressonthepharmacologicaleffectsandmechanismsofchuanxiong.ChineseJournalofNaturalMedicines,17(11),771–783.示例s:///10.1016/S1875-5364(19)30128-Chuanxiong,alsoknownasLigusticumchuanxiongHort,isatraditionalChinesemedicinethathasbeenusedforthousandsofyearstotreatvariousmedicalconditions,includingcardiovasculardisease(CVD).Chuanxiongalkaloids(CXAs)arethemainactiveingredientsofchuanxiong,whichhavebeenshowntopossessmultiplepharmacologicaleffects,suchasantiplateletaggregation,anti-inflammatory,antioxidant,andantiatherosclerosisactivities.

Asystematicreviewandmeta-analysisconductedbyHouetal.(2019)aimedtoevaluatetheefficacyandsafetyofCXAsforthetreatmentofCVD.Severaldatabasesweresearched,andatotalof21relevantrandomizedcontrolledtrials(RCTs)wereincludedintheanalysis.Themeta-analysisshowedthatCXAscouldsignificantlyreducetheincidenceofadversecardiovascularevents(ACEs),suchasmyocardialinfarctionandstroke,comparedtothecontrolgroup.CXAswerealsofoundtobeeffectiveinimprovingsymptomsandreducinginflammationmarkersinpatientswithstableanginapectoris(SAP).Moreover,CXAsshowedfavorablesafetyprofilesthroughoutthetrials.

AnotherreviewarticlebyZhuetal.(2019)summarizedtherecentresearchprogressonthepharmacologicaleffectsandmechanismsofchuanxiong.Apartfromtheaforementionedeffects,chuanxionghasbeenreportedtopossessneuroprotective,anticancer,andantiviralactivities.ThemechanismofCXAs’beneficialeffectsonCVDinvolvesmultiplepathways,includinginhibitingplateletactivation,reducingoxidative