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1、DeliveryofNerveGrowthFactortoBrainViaIntranasalAdministrationandEnhancementofBrainUptake1121SIVARAMKIRANVAKA,S.M.SAMMETA,LAINYB.DAY,S.NARASIMHAMURTHY1DepartmentofPharmaceutics,TheUniversityofMississippi,University,Mississippi386772DepartmentofBiology,TheUniversityofMis
2、sissippi,University,Mississippi38677Received10October2008;revised20November2008;accepted21November2008Publishedonline20January2009inWileyInterScience(www.interscience.wiley.com).DOI10.1002/jps.21674ABSTRACT:Themainobjectiveofthestudywastoinvestigatetheefficacyofchitosan
3、tofacilitatebrainbioavailabilityofintranasallyadministerednervegrowthfactor(NGF).InvitropermeabilitystudiesandelectricalresistancestudieswerecarriedoutacrossthebovineolfactoryepitheliumusingFranzdiffusioncells.ThebioavailabilityofintranasallyadministeredNGFinrathippoca
4、mpuswasdeterminedbycarryingoutbrainmicrodialysisinSprague–Dawleyrats.TheinvitropermeationfluxacrosstheolfactoryepitheliumofNGFsolutionwithoutchitosan(control)wasfoundtobe20.370.06ng/cm/h.Inpresenceofincreasingconcentrationofchitosan(0.1%,0.25%,and0.5%,w/v)thepermeation
5、fluxofNGFwasfoundtobe2.010.12,3.880.19,and24.120.21ng/cm/hrespectively.Trans-olfactoryepithelialelectricalresistancedecreased34.504.06%inpresenceof0.25%(w/v)chitosan.TheCmaxinratsadmi-nisteredwith0.25%(w/v)chitosanandNGFwas1008.62130.02pg/mL,whichwassignificantlyhi
6、gherthanthatforratsadministeredwithNGFonly97.3810.66pg/mL.Therewas14-foldincreaseinthebioavailabilityofintranasallyadministeredNGFwithchitosanthanwithoutchitosan.ChitosancanenhancethebrainbioavailabilityofintranasallyadministeredNGF.ß2009Wiley-Liss,Inc.andtheAmerican
7、PharmacistsAssociationJPharmSci98:3640–3646,2009Keywords:nervegrowthfactor;chitosan;nosetobrain;bioavailability;targeting;microdialysisINTRODUCTIONofneurotrophinsdirectlyintobraintissue(intraparenchymalorintracerebroventricularDeliveryoftherapeuticquantitiesofneurotro-
8、orintrathecaladministration)andcerebrospinal2phinstothebraininterstitialfluidisbelievedtofluidaretheonlymethodsinclinic
