甲氨蝶呤红细胞载体的制备与在大鼠体内药代动力学.研究

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1、couldenterintothecells．Wealsoreviewedthebrittlenessandchangeofthecellshape．3．TooptimizetheconditionforMTX—RBCperparation，wecalculatedandcomparedtheenvelopmentefficiencyofMTX—RBCwhichmeanstheproportionofMTXcontentincellstothetotalcontentunderdifferent

2、conditionslistedinb(34)orthogonalform，inordertoseekthebestarrangementindifferentconcentrationsofMTX，theratioofhypertonicglucoseandblood，timeofdehydrateandMTXsoakage．4．TheCrOSS-OVerdesignwasusedtoexplorethepharmacokineticsofvenousinjectionofMTX—RBCinr

3、atsandfinditspotentialclinicaluse．WestudypharmacokineticsinratsaftersingleivdoseofMTX—RBCandfreeMTX，bloodsampleswerecollectedat0，5，10，30，60，120，180，240，360，480,600，720and1440minutesafterdifferenttypesadministrationthendetermineddrugconcentrationinrat

4、plasmabyHPLC，calculatedthepharmcokineticparametersbyDASver1．0sofewaretofindoutwhetherithassustainedreleaseeffect．5．ToinvestigatethepreparationofMTX-RBCandfreeMTXandobserveitstissuedistributioninratsafter30,60，120,180，240,300rainadministration．Determi

5、neddrugconcentrationinheart，liver,spleen，lung,kidney,stomachandintestinetoseekwhetherMTX-RBCisadrug-targetingpreparationandCanarrivetocertaintissues．RESULTS：1．Thesamplewasquantifiedovertheconcentrationrangeof0．05．5．00／zg·ml。(r=O．9993)．Theminimaldetec

6、tableconcentrationWas20rig·ml～．Inter-dayRSDwere2％·7％andintra-dayRSDwere4％-10％respectively．Thismethodiseasy,sensitiveandaccuratefordeterminationofMTXconcentrationinplasmaofbothhumanandrats．2．TheenvelopmentefficiencytestresultsshowedthatthehigIlestenve

7、lopmentefficiencyineachlevelappearedthatthebestarrangement：theratioofwholebloodto50％glucosesolutionis3：2，thedehydrationtimeis40min，theMTXsolutionconcentrationis250pg。ml一．andthere·enclosedtimeis30min，whichreach41．58％inhumanand54．69％inrats．3．Theosmolal

8、ityonfragilityofcarriererythrocytedidnotchangemuchduringthe．V．ABSTRA(jrpreparationthatcanbeshowedinthecurveofosmolalityonfragility．Normalerythroeytehastheshapeofbiconcavelenswithacentralareaofpallorundermicrograph．Thedehydrated—RBCissmallerinsizeandd