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1、PreparationandCharacterizationofPoly(ε-Caprolactone)NanospheresContainingtheLocalAnestheticLidocaineESTEFANIAVANGELIERAMOSCAMPOS,1NATHALIEFERREIRASILVADEMELO,1,2VIVIANEAPARECIDAGUILHERME,2ENEIDADEPAULA,2ANDREHENRIQUEROSA,´1DANIELERIBEIRODEARAUJO,´2,3LEON
2、ARDOFERNANDESFRACETO1,21DepartmentofEnvironmentalEngineering,SaoPauloStateUniversity,Sorocaba,SP,Brazil˜2DepartmentofBiochemistry,StateUniversityofCampinas,Campinas,SP,Brazil3HumanandNaturalSciencesCenter,FederalUniversityofABC(UFABC),SantoAndre,SP,Brazi
3、l´Received8January2012;revised4September2012;accepted5October2012Publishedonline25October2012inWileyOnlineLibrary(wileyonlinelibrary.com).DOI10.1002/jps.23350ABSTRACT:Theobjectiveofthisworkwastodevelopamodifiedreleasesystemforthelocalanestheticlidocaine(L
4、DC),usingpoly(g-caprolactone)(PCL)nanospheres(NSs),toimprovethepharmacologicalpropertiesofthedrugwhenadministeredbytheinfiltrationroute.Invitroexperimentswereusedtocharacterizethesystemandinvestigatethereleasemechanism.TheNSspresentedapolydispersionindexo
5、f0.072,anaveragediameterof449.6nm,azetapotentialof−20.1mV,andanassociationefficiencyof93.3%.ThereleaseprofilesshowedthatthereleaseofassociatedLDCwasslowerthanthatofthefreedrug.Atomicforcemicroscopyanalysesshowedthatthesphericalstructureoftheparticleswaspre
6、servedasafunctionoftime,aswellasafterthereleaseexperiments.CytotoxicityandpharmacologicaltestsconfirmedthatassociationwiththeNSsreducedthetoxicityofLDC,andprolongeditsanestheticaction.Thisnewformulationcouldpotentiallybeusedinapplicationsrequiringgraduala
7、nestheticrelease,especiallydentalprocedures.©2012WileyPeriodicals,Inc.andtheAmericanPharmacistsAssociationJPharmSci102:215–226,2013Keywords:lidocaine;nanospheres;polymericdrugcarrier;drugrelease;anestheticactivity;nanotechnology;poly(ε-caprolactone);cont
8、rolledrelease;nanoparticles;analgesiaINTRODUCTIONanestheticactivity.AswithotherLA,LDCcanin-duceadversesystemicreactionsinthenervousandLocalanesthetics(LAs)aredrugsthatpromotethere-cardiovascularsystems,includingvasodilatat
