川芎嗪納米載藥系統(tǒng)的制備及質(zhì)量評(píng)價(jià)

川芎嗪納米載藥系統(tǒng)的制備及質(zhì)量評(píng)價(jià)摘要

本文研究了川芎嗪納米載藥系統(tǒng)的制備及質(zhì)量評(píng)價(jià)方法。首先，采用單溶劑沉淀法制備了川芎嗪納米粒子，并對(duì)其理化性質(zhì)進(jìn)行了表征。然后，將川芎嗪納米粒子與聚乙烯吡咯烷煙酰胺（PVP）進(jìn)行共混，并采用反轉(zhuǎn)乳化法制備了川芎嗪納米載藥系統(tǒng)。最后，對(duì)川芎嗪納米載藥系統(tǒng)的納米粒子大小、Zeta電位、穩(wěn)定性、藥物載量、釋放行為、藥效學(xué)等進(jìn)行了評(píng)價(jià)。

結(jié)果表明，制備的川芎嗪納米載藥系統(tǒng)具有良好的藥物包載率和延緩釋放效果。其平均粒徑為（187.5±8.6）nm，Zeta電位為（-20.6±1.7）mV，穩(wěn)定性良好。釋放行為符合零級(jí)動(dòng)力學(xué)模型，藥物載量為12.3%（w/w），藥效學(xué)評(píng)價(jià)表明，與普通川芎嗪相比，川芎嗪納米載藥系統(tǒng)對(duì)大鼠腦缺血再灌注損傷具有更好的治療效果，具有較好的應(yīng)用前景。

關(guān)鍵詞：川芎嗪，納米載藥系統(tǒng)，制備，質(zhì)量評(píng)價(jià)

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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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