甲氨喋呤單載和甲氨喋呤與長春新堿雙載紅細胞的制備及體外活性研究.pdf

1、第二軍醫(yī)大學碩士學位論文甲氨喋呤單載和甲氨喋呤與長春新堿雙載紅細胞的制備及體外活性研究姓名：王宣申請學位級別：碩士專業(yè)：麻醉學（輸血）指導教師：錢寶華20050501摘要目的建立甲氨喋呤(Methotrexate，MTX)單藥及甲氨喋呤與氏春新堿(Vincristine，VCR)雙藥載體紅絀胞的制備方法，探索雙藥載體紅絀胞在臨床腫瘤化療中的麻用前景。方法塒健康成人m以改良低滲預膨脹法制備MTX單藥及MTXVCR雙藥載體ll’細胞，分析其

2、載藥量、生物學性狀、抗腫瘤活性，用臍血制備MTX單載紅綱胞。結果成人及臍血MTX單載紅細胞載藥參數良好。聯合栽藥時，MTX濃度對聯合載藥率起主要作用，VCR濃度改變并不影晌聯合載藥率。當MTXlomg／ml、VCRlmg／ml時聯合載藥效果最好，此時MTX、VCR包載率分別為(26324193)％和(6082503)％。雙載紅細胞生物學特性與MTX單載紅細胞無差別，對K562細胞有明顯抑制增殖和促進凋亡作用，與未載和單載紅細胞差異顯著。

3、結論雙載紅細胞總載藥率良好，殺傷腫瘤細胞效果明顯，紅細胞能夠作為雙藥聯合載體，臍血紅細胞載體具有～定可行性和廣闊應用前景。關鍵詞紅細胞；藥物載體；甲氨喋呤；長春新堿；生物學性狀；K562AbstractHealthyadultfre曲erythrocytesorcorderythrocyteswereusedtopreparecarriererythrocytesloadedwithⅣrIXlonelyorco—encapsulated

4、withVCRtogetherusingamodifiedhypotonicpre—swellingandisotonicresealingtechniqueTheentrapmentrateandrecoveryrateofhealthyadultandcordbloodMTXqoadederythrocytesaregoodTheconcentrationofMTXisimportantforefficiencyrateofco—e

5、ncapsulated，buttheconcentrationofVCRisaosignificantinferencetotheco—encapsulationItistheoptimalconcentrationwhenconcentrationofMTXis10mg／mlandconcentrationofVCRis1mg／mlmeanwhile，thetwodrugsentrapmentrateare(2632193)％and(

6、60，825，03)％respectivelyThetotalloadingparametersofMTXVCRIoadederythrocytesaleaswellasmonoloadederythrocytes，andco—encapsulatedismoreefficientininhibitingtheproliferationofK562cellscomparedwithun—loadederythrocytesandMTXl

7、oadederythrocytesErythrocytesarepracticallycapableforusingasco—encapsulateddeliverysystemoftwoantineoplasticagentssuchasMTXandVCRCorderythroc”escanbeusedasdragdeliverysystemandhavewideprospectintheclinicalapplication，Key