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1、ChemicalHydrolysisofPhospholipidsN.J.ZUIDAM~ANDD.J.A.CROMMELINReceivedNovember21,1994,fromtheDepatfmentofPharmaceutics,UtrechtInstituteforPharmaceuticalSciences,GroningenUtrechtInstituteforDrugExploration,UtrechtUniversity,P.0.Box80.082.3508TBUtrecht,T
2、heNetherlands.AcceptedforpublicationJune2,1995@.kineticsofliposomalphospholipids.6Untilnow,nosystematicAbstract0Hydrolysiskineticsofphospholipidsinliposomescomposedstudyhasbeenperformedontheeffectofchainlengthandofdimyristoylphosphatidylcholine(DMPC),d
3、ipalmitoylphosphatidylcholinelheadgrouponthehydrolysisofphospholipidsinliposomecholesterol(DPPC/CHOL)10/4(molarratio)andeggphosphatidylcholinedispersion^.^Alsotheeffectoftheorganizationofthe(EPC)atpH4.0anddifferenttemperaturescouldbedescribedbyphosphol
4、ipidstate(bilayers,micelles,gelphase,liquidphase,Arrheniuscurveswithoutbreaks.However,theArrheniuscurvesfortheetc.)onthehydrolysisprocessisstillunclear.Frakjaeretal.hydrolysisofliposomalDPPCanddistearoylphosphatidylcholine(DSPC)foundahigheractivationen
5、ergyindistearoylphosphatidyl-underthesameconditionswerebiphasic.Abreakwasobservedinthecholine(DSPC)liposomesatpH6.5forbilayersinthegelstatecurvesextendingoverabroadrangebeforeandaftertheknownTmofthanintheliquidcrystallinestate.3However,otherstudieseach
6、ofthesephospholipidsinliposomes(42and56"C,respectively).couldnotconfirmthis~bservation.~~~Furthermore,possibleTheactivationenergy(Ea)forthehydrolysisofliposomalDPPCandDSPCeffectsofdifferenttypesofwatersolubleandlipophilicbelowtheTmwassubstantiallylarge
7、rthantheEaforliposomalDMPC,additivestoliposomedispersionsonthehydrolysiskineticsDPPCICHOL10/4,andEPCanddecreasedwhenDPPCwasmixedwithofphospholipidshaveneverbeeninvestigatedinanappropri-CHOLina1014molarratio.Hardlyanyinfluenceofthepresenceofateway,excep
8、tforthosefewreferredtoabove.a-tocopherol,cryoprotectants(glucose,trehalose,sucrose,andpropyleneTherefore,theobjectivesofthisstudyaretoassessinmoreglycol),andthemajorhydrolysisproductslysophospholipidsandfattydetailfactorswhichinfluenceh
