甲氨喋呤單載和甲氨喋呤與長(zhǎng)春新堿雙載紅細(xì)胞的制備及體外活性研究.pdf

1、第二軍醫(yī)大學(xué)碩士學(xué)位論文甲氨喋呤單載和甲氨喋呤與長(zhǎng)春新堿雙載紅細(xì)胞的制備及體外活性研究姓名：王宣申請(qǐng)學(xué)位級(jí)別：碩士專業(yè)：麻醉學(xué)（輸血）指導(dǎo)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(yù)膨脹法制備MTX單藥及MTXVCR雙藥載體ll’細(xì)胞，分析其

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

3、結(jié)論雙載紅細(xì)胞總載藥率良好，殺傷腫瘤細(xì)胞效果明顯，紅細(xì)胞能夠作為雙藥聯(lián)合載體，臍血紅細(xì)胞載體具有～定可行性和廣闊應(yīng)用前景。關(guān)鍵詞紅細(xì)胞；藥物載體；甲氨喋呤；長(zhǎng)春新堿；生物學(xué)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