PHYTOSOMES: A NOVEL DRUG DELIVERY FOR HERBAL ...

Advantages and Disadvantages: Phytosomes enhances the absorption of lipid insoluble polar phytoconstituents through oral as well as topical ... InternationalJournalOfPharmaceuticalSciencesAndResearch AnInternationalJournalpublishedmonthly AnOfficialPublicationofSocietyofPharmaceuticalSciencesandResearch CategoriesMenu EditorialBoard CurrentIssues Archives InstructionstoAuthors ManuscriptSubmission ConferenceProceedings Home» PHYTOSOMES:ANOVELDRUGDELIVERYFORHERBALEXTRACTS PHYTOSOMES:ANOVELDRUGDELIVERYFORHERBALEXTRACTS HTMLFullText PHYTOSOMES:ANOVELDRUGDELIVERYFORHERBALEXTRACTS M.Sravanthi*andJ.ShivaKrishna DepartmentofPharmaceutics,MallaReddyInstituteofPharmaceuticalsciences,Kompally,Hyderabad,AndhraPradesh,India ABSTRACT: Noveldrugdeliverysystemisanovelapproachtodrugdeliverythataddressesthelimitationsofthetraditionaldrugdeliverysystems.OurcountryhasavastknowledgebaseofAyurvedawhosepotentialisonlybeingrealizedintherecentyears.Theeffectivenessofanyherbalmedicationisdependentonthedeliveryofeffectivelevelofthetherapeuticallyactivecompound.Severelimitationexistsintheirbioavailabilitywhenadministeredorallyortopically.Phytosomesarerecentlyintroducedherbalformulationsthatarebetterabsorbedandasaresultproducebetterbioavailabilityandactionsthantheconventionalphyto-moleculesorbotanicalextracts.Intherecentdays,mostoftheprevailingdiseasesandnutritionaldisordersaretreatedwithnaturalmedicines.Severalplantextractsandphytoconstituents,despitehavingexcellentbioactivityinvitrodemonstratelessornoinvivoactionsduetotheirpoorlipidsolubilityorimpropermolecularsizeorboth,resultinginpoorabsorptionandbioavailability.So,muchworkhasbeendirectedtowardsthedevelopmentofnewconceptinherbaldeliverysystemi.e.,“phytosomes”whicharebetterabsorbed,utilizedandasaresultproducebetterresultsthanconventionalherbalextractsowingtothepresenceofphosphatidylcholinewhichlikelypushesthephytoconstituentthroughtheintestinalepithelialcelloutermembrane,subsequentlyaccessingthebloodstreamphytosomeshaveimprovedpharmacokineticandpharmacologicalparameterwhichinresultcanadvantageouslybeusedinthetreatmentoftheacuteandchronicliverdiseaseoftoxicmetabolicorinfectiveoriginorofdegenerativenature Keywords: Phytosomes,Herbosomes,Silybin,Herbal INTRODUCTION:Noveldrugdeliverysystemisanovelapproachtodrugdeliverythataddressesthelimitationsofthetraditionaldrugdeliverysystems.OurcountryhasavastknowledgebaseofAyurvedawhosepotentialisonlybeingrealizedintherecentyears.However,thedrugdeliverysystemusedforadministeringtheherbalmedicinetothepatientistraditionalandout-of-date,resultinginreducedefficacyofthedrug.Ifthenoveldrugdeliverytechnologyisappliedinherbalmedicine,itmayhelpinincreasingtheefficacyandreducingthesideeffectsofvariousherbalcompoundsandherbs.Thisisthebasicideabehindincorporatingnovelmethodofdrugdeliveryinherbalmedicines.Thus,itisimportanttointegratenoveldrugdeliverysystemandIndianAyurvedicmedicinestocombatmoreseriousdiseases.Foralongtimeherbalmedicineswerenotconsideredfordevelopmentasnovelformulationsowingtolackofscientificjustificationandprocessingdifficulties,suchasstandardization,extractionandidentificationofindividualdrugcomponentsincomplexpolyherbalsystems. However,modernphytopharmaceuticalresearchcansolvethescientificneeds(suchasdeterminationofpharmacokinetics,mechanismofaction,siteofaction,accuratedoserequiredetc.)ofherbalmedicinestobeincorporatedinnoveldrugdeliverysystem,suchasnanoparticles,microemulsions,phytosomes,matrixsystems,soliddispersions,liposomes,solidlipidnanoparticlesandsoon.Inthepast,almostallthemedicineswerefromtheplants;theplantbeingman'sonlychemistforages.Herbsarestagingacomeback,herbal‘renaissance’ishappeningallovertheglobeandmoreandmorepeoplearetakingnoteofherbaltherapiestotreatvariouskindsofailmentsinplaceofmainstreammedicine.Therearethreemainreasonsforthepopularityofherbalmedicines: Thereisagrowingconcernovertherelianceandsafetyofdrugsandsurgery. Modernmedicineisfailingtoeffectivelytreatmanyofthemostcommonhealthconditions. Manynaturalmeasuresarebeingshowntoproducebetterresultsthandrugsorsurgery     withoutthesideeffects. Alsothereisincreasingevidencethatmanycurrentdrugtherapiessimplysuppresssymptomsandignoretheunderlyingdiseaseprocesses.Incontrast,manynaturalproductsappeartoaddressthecauseofmanydiseasesandyieldsuperiorclinicalresults.Unfortunately,mostphysiciansandpatientsarenotawarethatthesenaturalalternativesexist.Somedrugshaveanoptimumconcentrationrangewithinwhichmaximumbenefitisderived,andconcentrationsaboveorbelowthisrangecanbetoxicorproducenotherapeuticbenefitatall. Ontheotherhand,theveryslowprogressintheefficacyofthetreatmentofseverediseaseshassuggestedagrowingneedforamultidisciplinaryapproachtothedeliveryoftherapeuticstotargetsintissues.Fromthis,newideasoncontrollingthepharmacokinetics,pharmacodynamics,non-specifictoxicity,immunogenicity,bio-recognitionandefficacyofdrugsweregenerated.Thesenewstrategies,oftencalleddrugdeliverysystems(DDS),arebasedoninterdisciplinaryapproachesthatcombinepolymerscience,pharmaceutics,bioconjugatechemistry. Noveldrugdeliverysystemisanovelapproachtodrugdeliverythataddressesthelimitationsofthetraditionaldrugdeliverysystems.Modernmedicinecuresaparticulardiseasebytargetingexactlytheaffectedzoneinsideapatient'sbodyandtransportingthedrugtothatarea.Noveldrugdeliverysystemattemptstoeliminateallthedisadvantagesassociatedwithconventionaldrugdeliverysystems.Therearevariousapproachesbywhichnoveldrugdeliverycanbeachieved. AdvantagesofHerbalMedicines: Herbalmedicinesareverycheapincomparisontotheconventionalformofmedication.It’ssomethingwhicheverypocketcanafford,unlikeotherformsofmedicationwhichcancreateabigholeinyourwallet. Herbalmedicinesareknowntobemoreproductiveincomparisontootherformsofmedicationincuringcertainconditions.Unlessmixedwithotherchemicalcomponents,theyareknowntobeallnatural. Oneofthegreatestbenefitassociatedwithherbalmedicineisthelessexistenceofsideeffects.Also,theytendtoofferlonglastingbenefitsintermsofoverallwellness. Obesityisagrowingproblemwhichisknowntohavehazardousissuesonanindividual’shealth.Herbalmedicinecanhelponedealwiththeproblemofobesityveryeffectivelywithoutconsumingmuchtimeandefforts. DisadvantagesofHerbalMedicines: Insomeinstances,individualsswitchtoherbalmedicationwithoutrealizingthatthesymptomscanbelinkedtoadifferentailment.Unlike,conventionalmedicationwhichinvolvesconstantmonitoringofyourhealth,herbalmedicinesaretakenwithoutprescriptionwhichmeansthatinsomecases,individualmightbeundergoingatrialanderrorprocesswiththeirmedication. Althoughherbalmedicineshasthepotentialtocuremanyailments,thecuringperiodisusuallylongerincomparisontoconventionalmedication.Oneneedstohaveimmensepatiencewhileundergoingherbaltreatment. Herbalmedicinescancauseallergicreactionsinsomecases.Beforeresortingtoherbalmedicationyouneedtoensurethatyouarenotallergictotheparticularherbthatyouwillbeconsuming.Conventionalmedicationcanalsocauseallergicreactions,buttheyareusuallytakenuponprescriptionswhichiswhythechancesofallergicreactionsareless. Thegovernmentdoesnotapproveofanykindofherbalmedication.It’susuallyconsumedupontheperson’sownrisk,andwhenitcomestobrandedherbalsupplementsonecan’texpectanykindofqualityassurance Phytosomes:Theeffectivenessofanyherbalmedicationisdependentonthedeliveryofeffectivelevelofthetherapeuticallyactivecompound.Severelimitationexistsintheirbioavailabilitywhenadministeredorallyortopically.Phytosomes arerecentlyintroducedherbalformulationsthatarebetterabsorbedthanextracts.Theterm"phyto"meansplant,while"some"meanscell‐like.Overthepastcentury;phytochemicalandphyto‐pharmacologicalsciencesestablishedthecompositions,biologicalactivitiesandhealthpromotingbenefitsofnumerousbotanicalproducts.Mostofthebiologicallyactiveconstituentsofplantsarepolarorwatersolublemolecules.However,watersolublephytoconstituents(likeflavonoids,tannins,glycosidicaglyconesetc)arepoorlyabsorbedeitherduetotheirlargemolecularsizewhichcannotabsorbbypassivediffusion,orduetotheirpoorlipidsolubility;severelylimitingtheirabilitytopassacrossthelipid‐richbiologicalmembranes,resultingpoorbioavailability1. Phytomedicines,complexchemicalmixturespreparedfromplants,havebeenusedforhealthmaintenancesinceancienttimes.Butmanyphytomedicinesarelimitedintheireffectivenessbecausetheyarepoorlyabsorbedwhentakenbymouth.ThePhytosome®technology,developedbyIndenaS.p.A.ofItaly,markedlyenhancesthebioavailabilityofselectphytomedicines,byincorporatingphospholipidsintostandardizedextractsandsovastlyimprovetheirabsorptionandutilization2. Overthepastcentury,chemicalandpharmacologicscienceestablishedthecompositions,biologicalactivitiesandhealthgivingbenefitsofnumerousplantextracts.Butoftenwhenindividualcomponentswereseparatedfromthewholetherewaslossofactivitythenaturalingredientsynergybecamelost3. Standardizationwasdevelopedtosolvethisproblem.Asstandardizedextractsbecameestablished,poorbioavailabilityoftenlimitedtheirclinicalutility.Then,itwasdiscoveredthatcomplexationwithcertainotherclinicallyusefulnutrientssubstantiallyimprovedthebioavailabilityofsuchextracts.Thenutrientssohelpfulforenhancingtheabsorptionofothernutrientsarethephospholipids.Phospholipidsarecomplexmoleculesthatareusedinallknownlifeformstomakecellmembranes.Theyarecellmembranebuildingblocks,makingupthematrixintowhichfitalargevarietyofproteinsthatareenzymes,transportproteins,receptors,andotherbiologicalenergyconverters.Inhumansandotherhigheranimalsthephospholipidsarealsoemployedasnaturaldigestiveaidsandascarriersforbothfat‐miscibleandwatermisciblenutrients4. Increasedbioavailabilityofthephytosomesoverthesimpler,noncomplexplantextractshasbeendemonstratedbypharmacokinetic(tissuedistribution)andactivitystudies,conductedinanimalsaswellasinhumans.Phytosomeshasanaddeddimensiontheprovenhealthgivingactivityofthephospholipidsthemselves.PhytosomeisalsooftenknownasHerbosomes5.Phytosomesexhibitbetterpharmacokineticandpharmacodynamicprofilethanconventionalherbalextracts.MolecularlayerconsistingofPCandotherphospholipidsprovidesacontinuousmatrixintowhichtheproteinsinsert(figure1). FIGURE1:CELLMEMBRANESARELARGELYLIPIDPHASE AdvantagesandDisadvantages: Phytosomesenhancestheabsorptionoflipidinsolublepolarphytoconstituentsthroughoralaswellastopicalrouteshowingbetterbioavailability,hencesignificantlygreatertherapeuticbenefit. Astheabsorptionofactiveconstituent(s)isincreased,soitsdoserequirementisreduced. Phosphatidylcholineusedinpreparationofphytosomes,besidesactingasacarrieralsoactsasahepatoprotective.  Incaseofphytosomes.Chemicalbondsareformedbetweenphosphatidylcholinemoleculeandphytoconstituent,sotheyshowbetterstabilityprofilethanliposome. Applicationofphytoconstituentsinformofphytosomeimprovetheirpercutaneousabsorptionandactasfunctionalcosmetics. Disadvantage: Phytoconstituentfromphytosomesarerapidlyeliminated. MechanismofPhytosomeTechnology6: Phytosomesresultsfromthereactionofastoichiometricamountofthephospholipid(phosphatidylcholine)withthestandardizedextractorpolyphenolicconstituents(likesimpleflavonoids)inanaproticsolvent7.Phosphatidylcholineisabifunctionalcompound,thephosphatidylmoietybeinglipophilicandthecholinemoietybeinghydrophilicinnature.Specificallythecholineheadofthephosphatidylcholinemoleculebindstothesecompoundswhilethelipidsolublephosphatidylportioncomprisingthebodywhichthenenvelopesthecholineboundmaterial. Hence,thephytomolecules(figure2)producealipidsolublemolecularcomplexwithphospholipids,alsocalledasphyto‐phospholipidcomplex.Moleculesareanchoredthroughchemicalbondstothepolarcholineheadofthephospholipids,ascanbedemonstratedbyspecificspectroscopictechniques8,9.Precisechemicalanalysisindicatestheunitphytosomeisusuallyaflavonoidmoleculelinkedwithatleastonephosphati-dylcholinemolecule. FIGURE2:AFLAVONOIDMOLECULEISENVELOPEDBYAPHOSPHOLIPID MOLECULE Thephytosometechnologyproducesalittlecell,wherebytheplantextractoritsactiveconstituentisprotectedfromdestructionbygastricsecretionsandgutbacteriaowingtothegastroprotectivepropertyofphosphatidylcholine10. Differencebetweenliposomeandphytosomes:Aliposomeisformedbymixingawatersolublesubstancewithphosphatidylcholineindefiniteratiounderspecificconditions.Here,nochemicalbondisformed;thephosphatidylcholinemoleculessurroundthewatersolublesubstance.Theremaybehundredsoreventhousandsofphosphatidylcholinemoleculessurroundingthewater‐solublecompound.Incontrast,withtheherbosomeprocessthephosphatidylcholineandtheplantcomponentsactuallyforma1:1ora2:1molecularcomplexdependingonthesubstance(s)complexed,involvingchemicalbonds(hydrogenbonds).Thisdifferenceresultsinphytosomebeingmuchbetterabsorbedthanliposomesshowingbetterbioavailability.phytosomeshavealsobeenfoundsuperiortoliposomesintopicalandskincare(cosmetic)products11. Phytosomesarenotliposomes‐structurally,thetwoaredistinctlydifferentasshowninFig.Thephytosomeisaunitofafewmoleculesbondedtogether,whiletheliposomeisanaggregateofmanyphospholipidmoleculesthatcanencloseotherphytoactivemoleculesbutwithoutspecificallybondingtothem12,13.Thisdifferenceresultsinphytosomebeingmuchbetterabsorbedthanliposomesshowingbetterbioavailability.Phytosomeshavealsobeenfoundsuperiortoliposomesintopicalandskincare(cosmetic)products. Inliposomes,theactiveprinciplesarewatersolubleandarehostedintheinnercavity,withlittle,ifany,interactiontakingplacebetweenthehydrophilicprincipleandthesurroundinglipidcore.Conversely,phytosome’shosttheirpolyphenolicguest,generallylittlesolublebothinwaterandinlipids,attheirsurfacewherethepolarfunctionalitiesofthelipophilicguestinteractviahydrogenbondsandpolarinteractionswiththechargedphosphateheadofphospholipids,formingauniquearrangementthatcanbeevidencedbyspectroscopy.Thephytosomeformulationalsoincreasestheabsorptionofactiveingredientswhentopicallyappliedontheskin,andimprovessystemicbioavailabilitywhenadministeredorally.Inwatermedium,aphytosomewillassumeamicellarshape,formingasphericalstructure,overallsimilartoaliposome,butwithadifferentguestlocalization14. FIGURE3:DIFFERENCEBETWEENLIPOSOMEANDPHYTOSOME PreparationMethods: Phytosomesarenovelcomplexeswhicharepreparedbyreactingfrom3‐2molesbutpreferablywithonemoleofanaturalorsyntheticphospholipid,suchasphosphatidylcholine,phosphatidylethanolamineorphosphatidyiserinewithonemoleofcomponentforexample‐flavolignanans,eitheraloneorinthenaturalmixtureinaproticsolventsuchasdioxaneoracetonefromwhichcomplexcanbeisolatedbyprecipitationwithnonsolventsuchasaliphatichydrocarbonsorlyophilizationorbyspraydrying.Inthecomplexformationofphytosomestheratiobetweenthesetwomoietiesisintherangefrom0.5‐2.0moles.Themostpreferableratioofphospholipidtoflavonoidsis1:1. Naringenin-phosphatidylcholinephytosome:Naringenin–PCcomplexwaspreparedbytakingnaringeninwithanequimolarconcentrationofphosphatidylcholine(PC).TheequimolarconcentrationofPCandnaringeninwereplacedina100mLroundbottomflaskandrefluxedindichloromethanefor3hrs.Onconcentratingthesolutionto5–10mL,30mLofn‐hexanewasaddedtogetthecomplexasaprecipitatefollowedbyfiltration.Theprecipitatewascollectedandplacedinvacuumdesiccators15,16. Silybin-PhospholipidComplexPreparation:Therequiredamountsofdrugandphospholipidswereplacedina100mlround‐bottomflaskanddissolvedinanhydrousethanol.Afterethanolwasevaporatedoffundervacuumat40C,thedriedresiduesweregatheredandplacedindesiccatorsovernight,thencrushedinthemortarandsievedwitha100mesh.Theresultantsilybin–phospholipidcomplexwastransferredintoaglassbottle,flushedwithnitrogenandstoredintheroomtemperature17. FIGURE4:MAINSTEPSINPREPARATIONOFPHYTOSOMES PropertiesofPhytosomes:Thetermphytosomeisusedtodefineacomplexbetweenanaturalproductandnaturalphospholipids,likesoyphospholipidsthatareobtainedbythereactionofstoichiometricamountsofphospholipidsandphytoconstituentsinanappropriatesolvent.Spectroscopicdatarevealthatthemainphospholipid‐substrateinteractionisduetotheformationofhydrogenbondsbetweenthepolarheadofthephospholipids(i.e.,phosphateandammoniumgroups)andthepolarfunctionalitiesofthesubstrate. Phytosomescanaccommodatetheactiveprinciplethatisanchoredtothepolarheadofthephospholipids,becominganintegralpartofthemembrane.Forexample,incaseofthecatechindistearoyl PCcomplex,thereisformationofH‐bondsbetweenthephenolichydroxylsoftheflavonesmoietyandthephosphateiononthePCside18. Phosphotidylcholine:Studyofcomparisonsofnuclearmagneticresonanceofthecomplexwiththoseofthepureprecursorsindicatesthatthesignalsofthefattychainarealmostunchanged.Suchevidencesinferredthatthetwolongaliphaticchainsarewrappedaroundtheactiveprinciple,producingalipophilicenvelopethatshieldsthepolarheadofthephospholipidandthecatechin19. Phytosomesareadvancedformsofherbalproductsthatarebetterabsorbed,utilizedand,asaresult,producebetterresultsthanconventionalbotanicalherbalextracts.Theincreasedbioavailabilityofthephytosomeoverthenon‐complexedbotanicalderivativeshasbeendemonstratedbypharmacokineticstudiesorbypharmacodynamictestsinexperimentalanimalsandinhumansubjects20. Phytosomesarelipophilicsubstanceswithadefinitemeltingpoint,freelysolubleinnon‐polarsolvents,andmoderatelysolubleinfats21. Whentreatedwithwater,theyassumeamicellarshape,formingstructuresthatresembleliposomes      exhibitingfundamentaldifferences22. EvaluationofPhytosomes23,24,25,26: Characterizationtechnique: Visualization:Visualizationofphytosomescanbeachievedusingtransmissionelectronmicroscopy(TEM)andbyscanningelectronmicroscopy(SEM). Vesiclesizeandzetapotential:Theparticlesizeandzetapotentialcanbedeterminedbydynamiclightscattering(DLS)usingacomputerizedinspectionsystemandphotoncorrelationspectroscopy(PCS). Entrapmentefficiency:Theentrapmentefficiencyofadrugbyphytosomescanbemeasuredbytheultracentrifugationtechnique23. Transitiontemperature:Thetransitiontemperatureofthevesicularlipidsystemscanbedeterminedbydifferentialscanningcalorimeter24. Surfacetensionactivitymeasurement:ThesurfacetensionactivityofthedruginaqueoussolutioncanbemeasuredbytheringmethodinaDuNouyringtensiometer. Vesiclestability:Thestabilityofvesiclescanbedeterminedbyassessingthesizeandstructureofthevesiclesovertime.ThemeansizeismeasuredbyDLSandstructuralchangesaremonitoredbyTEM25. Drugcontent:Theamountofdrugcanbequantifiedbyamodifiedhighperformanceliquidchromatographicmethodorbyasuitablespectroscopicmethod. Spectroscopicevaluations:Toconfirmtheformationofacomplexortostudythereciprocalinteractionbetweenthephytoconstituentandthephospholipids,thefollowingspectroscopicmethodsareused. 1HNMR:TheNMRspectraof(+)‐catechinanditsstoichio‐metriccomplexwithdistearoylphosphatidylcholinehavebeenstudiedbyBombardellietal.,26.Innonpolarsolvents,thereisamarkedchangeofthe1H‐NMRsignaloriginatingfromtheatomsinvolvedintheformationofthecomplex,withoutanysummationofthesignalpeculiartotheindividualmolecules.Thesignalsfromtheprotonsbelongingtotheflavonoidsaretobebroadenedthattheprotoncannotberelieved.Inphospholipids,thereisbroadeningofallthesignalswhilethesingletcorrespondingtotheN‐(CH3)3ofcholineundergoesanupliftshift.Heatingthesampleto60˚resultsintheappearanceofsomenewbroadbands,whichcorrespondmainlytotheresonanceoftheflavonoidmoiety. 13CNMR:Inthe13C‐NMRspectrumof(+)‐catechinanditsstoichiometriccomplexwithdistearoylphosphatidylcholine,particularlywhenrecordedinC6D6atroomtemperature,alltheflavonoidcarbonsareclearlyinvisible.Thesignalscorrespondingtotheglycerolandcholineportionofthelipid(between60–80ppm)arebroadenedandsomeareshifted,whilemostoftheresonancesofthefattyacidchainsretaintheiroriginalsharplineshape.Afterheatingto60˚,allthesignalsbelongingtotheflavonoidmoietiesreappear,althoughtheyarestillverybroadandpartiallyoverlapping. FTIR:TheformationofthecomplexcanbealsobeconfirmedbyIRspectroscopybycomparingthespectrumofthecomplexwiththespectrumoftheindividualcomponentsandtheirmechanicalmixtures.FTIRspectroscopyisalsoausefultoolforthecontrolofthestabilityofphytosomeswhen   micro‐dispersedinwaterorwhenincorporatedinverysimplecosmeticgels.Fromapracticalpointofview,thestabilitycanbeconfirmedbycomparingthespectrumofthecomplexinsolidform(phytosomes)withthespectrumofitsmicrodispersioninwaterafterlyophilization,atdifferenttimes.Inthecaseofsimpleformulations,itisnecessarytosubtractthespectrumofthecosmeticformatdifferenttimes,comparingtheremainingspectrumofthecomplexitself. Invitroandinvivoevaluations: Modelsofin‐vitroandin‐vivoevaluationsareselectedonthebasisoftheexpectedtherapeutic activityofbiologicallyactivephytoconstituentspresentinthephytosomes.27,28.Forexample,in-vitroantihepatotoxicactivitycanbeassessedbytheantioxidantandfreeradicalscavengingactivityofthephytosomes29.Forassessingantihepatotoxicactivityin‐vivo,theeffectofpreparedphytosomesonanimalsagainstthioacetamideparacetamolor,alcohol‐inducedhepatoxicitycanbeexamined30,31.Skinsensitizationandtolerabilitystudiesofglycyrrhetinicacid‐Phytosome®ointment,acommercialproduct,describetheinvivosafetyevaluationmethodology32. Applicationsofphytosomes33,34,35,36,37:Differentphytosomeproductshavedemonstratedsignificanttherapeuticeffectswhencomparedwiththeconventionalherbalextracts. TABLE1:COMMERCIALPHYTOSOMESPREPARATION19, 39, 40, 41, 42 PhytosomesPhosphatidyicholine Phytoconstituent complexed Indication Dose SilybinPhytosome Silybinfromsilymarinmarium Nutraceutical,antioxidantforLiverandskin 120mg GinkgoPhytosome 24%ginkgoflavonoidsfromGinkgobiloba Protectbrainandvascularlining 120mg OliveoilPhytosome PolyphenolsfromEuropaeaoil Antioxidant,antiinflammatory,Anti-hyperlipidemic - Grapeseedphytosome ProcynidinsfromVitisvinifera Nutraceutical,systemicantioxidant 50-100mg HawthornPhytosome Flavonoidsfromcarteagussp. Nutraceutical,cardioprotective,Antihypertensive 100mg CentellaPhytosome Terpenes Veinandskindisorders - Ecdhinacea  Phytosome EchinacosidefromEchinaceaaugustifolia Nutraceutical,immunomodulator -  RecentresearchonSilybummarianum:Recentresearchshowsenhancedabsorptionandbioavailabilitywithphytosomescomparedwiththe  conventionaldeliverysystems. MostoftheherbosomestudiesarefocusedonSilybummarianum(Milkthistle),whichcontainspremierliverprotectantflavonoids.Silymarinprimarilycontainsthreeflavonoidsofthesubclassflavonol(havingafullysaturatedC‐ring). Silybinpredominates,followedbysilydianinandsilychristin.Silybinisactuallyaflavonolignan,probablywithintheplantbythecombinationofaflavonolwithaconiferylalcohol. Silybinisthemostpotentofthethree,Silymarinhasbeenshowntohavepositiveeffectsintreatingliverdiseasesofvariouskinds,includinghepatitis.cirrhosis,fattyinfiltrationoftheliver(chemical‐andalcoholinducedfattyliver),andinflammationofthebileduct38. TheantioxidantcapacityofSilymarinsubstantiallybooststheliver'sresistancetotoxicchemicalsthefruitoftheMilkthistleplantcontainsflavonoidsknownforhepatoprotectiveeffects,astandardizedextractfromSilybummarinumisanexcellentliverprotectantbutispoorlyabsorbedorally.Silybinprotectstheliverbyconservingglutathioneintheparenchymalcells,whilePChelpstorepairandreplacecellmembranes. Theseconstituentsarelikelytoofferthesynergisticbenefitofsparinglivercellsfromdestruction.InitsnativeformwithintheMilkthistlefruit,Silybinoccursprimarilycomplexedwithsugars,asaflavonylglycosideorflavonolignan.Silybinhasbeenextensivelyresearchedandfoundtohaveimpressivebioactivity,althoughlimitedbypoorbioavailability. Tedescoetal.,39reportedthattheSilymarinphytosomesshowbetteranti‐hepatotoxicactivitythanSilymarinaloneandcanprovideprotectionagainstthetoxiceffectsofAflatoxinB1ontheperformanceofBroilerchicks.Busbyetal.reportedthattheuseofaSilymarinphytosomeshowedabetterfetoprotectantactivityfromethanol‐inducedbehavioraldeficitsthanuncomplexedSilymarinGrangeetal.conductedaseriesofstudiesontheSilymarinphytosomecontainingastandardizedextractfromtheseedsofSilybummarinumadministeredorallytoanimalsandfoundthatitcouldprotectthefetusfrommaternallyingestedethanol. Yanyuetal.,40preparedtheSilymarinphytosomeandstudieditspharmacokineticsinrats.Inthestudy,thebioavailabilityofSilybininratswasincreasedremarkablyafteroraladministrationofthepreparedSilybin‐phospholipidcomplexduetoanimpressiveimprovementofthelipophilicpropertyoftheSilybin‐phospholipidcomplexandimprovementofthebiologicaleffectofSilybinBarzaghietal.conductedahumanstudydesignedtoassesstheabsorptionofSilybinwhendirectlyboundtoPC.TheplasmaSilybinlevelsweredeterminedafteradministrationofasingleoraldoseofSilybinphytosomeandasimilaramountofSilybinfromMilkthistletohealthyvolunteers.TheresultsindicatedthattheabsorptionofSilybinfromtheSilybinphytosomeisapproximatelyseven‐timesgreatercomparedwiththeabsorptionofSilybinfromtheregularMilkthistleextract(70‐80%Silymarincontent). GinkgoselectPhytosomevsGinkgobilobaExtract:ThepharmacokineticprofileofGinkgoselectRPhytosomehasbeendefinedinexperimentalanimals41,42andinhumanvolunteers.ItsbioavailabilityhasbeencomparedtoGBE.FifteenhealthyvolunteerswererandomlydividedintotwogroupsandadministeredrespectivelywithGinkgoselectRandGinkgoselectRPhytosome,providingboth9.6mgoftotalterpenelactones.Thesubjectsswitchedformulationsafteraweekofwashout.Bloodsampleswerecollectedat30,60,120,180,240,300and400minafteringestion.Terpenelactonesdetectionwasperformedbymeansofliquidchromatography/atmosphericpressurechemicalionizationmassspectrometry(LC/APCI-ITMS).GinkgolidesA,Bandbilobalidewereabsorbedtoahigherextent(aboutthree-fold)afteradministrationofGinkgoselectRPhytosome(figure5). FIGURE5:GINKGOSELECTPHYTOSOMEVSGINKGOBILOBAEXTRACT 18-ßGlycyrrheticacidPhytosomevs18-ßGlycyrrheticacid:Finallyasanexample,anactivitycomparisonbetweenthePhytosomeandnonPhytosomeformbytopicalapplicationisreportedaswell43.Theinflammatoryresponseofthe18β-GlycyrrheticAcidPhytosomewereassessedintheexperimentalmodelofCrotonoil-inducedoedemareduction.Atthesamedose(0.16μM),theactionofthe18β-GlycyrrheticAcidPhytosomewasfoundtobegreaterandtolastlongerthanthatof18β-glycyrrheticacidalone. ThismeansthatthePhytosomenotonlyincreasestheactiveingredienttolerabilityandabsorption,butalsoimprovesitsefficacy(figure6). FIGURE6:18βGLYCYRRHETICACIDPHYTOSOMEVS18βGLYCYRRHETICACID HerbalDrugsusedforthemanagementofperiodentaldisease: AcaciaCatechuWild44,45:AcaciacatechuWild.(Fam.Mimosae,Hindi-Khair,English-Citchtree,Sanskrit-Khadira)iswidelyusedinAyurvedaformanydiseasesandmainlyforskindiseases.A.catechucommonlyknownasBlackkhairandcommerciallyusedtoobtainKatthainNorthIndia.ItfoundwidelydistributedinJammu,Punjab,HimachalPradesh,U.P.,M.P.,Bihar,A.P.andMaharashtra.A.catechuisusedasmouthwashformouth,gumandthroatdiseaselikegingivitis,stomatitis.Katthaiscooling,digestive,astringent,bleedingpiles,uterinehemorrhages,leucorrhoea,atonicsdyspepsia,chronicbronchitis,etc.thedecoctionofbarkmixedwithmilkistakentocureandcough. AloeVeraMiller46,47: AloeveraisAloebarbadensisMiller.(Fam.Liliaceae).Itisshrubbyorarborescent,perennial,xerophytic,pea-greencolourplant.ItgrowsmainlyinthedryregionofAfrica,Asia,EuropeandAmerica.InIndiaitisfoundinRajasthan,A.P.,Gujarat,MaharashtraandTamilnadu.Thespeciesisfrequentlyusedinherbalmedicineandcosmetics.ManyscientificstudiesfortheuseofextractsofAloeverahavebeenundertaken.(48-49)Traditionally,Aloewasusedtopicallytohealwounds,skindiseasesandorallyasaluxative.Itisalsousedinconditionsincludingdiabetes,asthma,epilepsyandosteoarthritis.Aloeveragelusedinlotionsandsunblocks.FDAhasapprovedasanaturalfoodflavoringagent OcimumSanctumL.(Tulsi)48,49:InAyurveda,Tulsi(OcimumsanctumL.)hasbeenwelldocumentedforitstherapeuticpotentialsanddescribedasDashemaniShwasaharni(antiasthmatic)andantikaphicdrugs(Kaphaghna).Although,thetraditionalmedicalpractitionersinIndiahavebeenwidelyusingthismedicinalplantformanagementofvariousdiseaseconditionsfromancienttime16.Tulsiisusedtocontroldiabetes17.Pasteof leavesisfoundeffectiveinthetreatmentofringwormandotherskindiseases18.Itisrecommendedasantidotefordogbite,scorpionbiteandinsectbiteintraditionalsystemofmedicine.Theseedaremucilaginousanddemulcentandgivenindisordersofthegenitourinarysystem.Theleaveshavealsobeen showntopossessgoodanti-stressandanalgesicactivity. CurcumaLonga(Turmeric)50,51:TurmericcommonlyknownasHaldiandhasbeenusedforthousandsofyearsasadye,aflavoringandamedicinalherb.ItisarhizomatousherbaceousperennialplantoffamilyZingiberaceae.ItisnativetotropicalSouthAsiaandneedstemperaturesbetween20°Cand30°C.Haldiisaperennialplantwithorange,oblongtubers2or3inchesinlengthandoneinchindiameter,pointedortaperingatonend.Whendried,itismadeintoayellowpowderwithabitter,slightlyacrid,yetsweettaste.InIndia,ithasbeenusedtraditionallyasaremedyforstomachandliverailments,aswellastopicallytohealsores.AncientIndianmedicinehastoutedturmericasanherbwiththeabilitytoprovideglowandlustertotheskinaswellasvigorandvitalitytotheentirebody CONCLUSION:Thisreviewisanattempttopresentaconciseprofileofphytosomesasadeliverysystem.Herbosomesarenovelformulationswhichofferimprovedbioavailabilityofhydrophilicfavonoidsandothersimilarcompoundsthroughtheskinorgastrointestinaltract.Theyhavemanydistinctiveadvantagesoverotherconventionalformulations.Theformulationmethodologyforphytosomeissimpleandcanbeeasilyupgradedtoacommercialscale. 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RamirezS,BoscaA,SolerA,GutierrezMA:Antioxidantcurcumaextractsdecreasethebloodlipidperoxidelevelsofhumansubjects1995;18:167-169.MaitiK,MukherjeeK,GantaitA,SahaBP,MukherjeePK:Curcumin‐phospholipidcomplex-Preparation,therapeuticevaluationandpharmacokinetic Howtocitethisarticle: SravanthiMandKrishnaJS:Phytosomes:ANovelDrugDeliveryforHerbalExtracts.IntJPharmSciRes.2013;4(3);949-959 studyinrats.IntJPharmPharmacol2007;330:152‐63.   ArticleInformation SrNo: 8 PageNo: 949-959 Size: 873KB Download: 3270 CitedBy: 7 Language: English Licence: IJPSR Authors: M.Sravanthi*andJ.ShivaKrishna AuthorsAddress: DepartmentofPharmaceutics,MallaReddyInstituteofPharmaceuticalsciences,Kompally,Hyderabad,AndhraPradesh,India Email: [email protected] Received: 25November,2012 Revised: 30December,2012 Accepted: 14February,2012 DOI: http://dx.doi.org/10.13040/IJPSR.0975-8232.4(3).949-59 Published: 01March,2013 Download Home AboutUs EditorialBoard CurrentIssues InstructionstoAuthors ManuscriptSubmission ContactUs Gallery ManuscriptTracking All©2022arereservedbyInternationalJournalofPharmaceuticalSciencesandResearch ThisJournallicensedunderaCreativeCommonsAttribution-NonCommercial-ShareAlike3.0UnportedLicense