GSH感巯嘌呤—羧甲基壳聚糖高分子前药的制备与性能研究.docx

A b A b str a c t A m PhiP hilie P olym erie Pro drugs h av e b een ap Plied in t切叮or theraP y for 油 p rov ing tar g cting an d b io av ailab ility o f d rug s，redu e ing sid e effe cts o f ant i~tum o r 山”9 5，etc . E sp eeially，the se P rodru gs eonsisting o f 坤 dro Phi lie an d 勿 droPh ob ie se g 叮e n ts e a n f o r m se lf -a s se m b lie s w h ic h e a n a v o id t h e r et ie u l o e n d o t h e lia l sy s te m (R E S ) b eeaus e o f the sm all nano 一size. C ov alently b o n ded d isul fid es ean b e form ed sPon加m eous ly b y auto劝dat ion o f su lthy 卿 15，Prim a rily v ia o 劝d ation uP on ex P osure to air， 从七ich ean rev ersib ly b e eleav ed in the P resenc e o f redu eing ag enis suc h as glu tal[hi o n e (G S H ，2一10 m M ) in the eells. It 诚 11 b e v ery P ro而 sing in eanc er tre atln ent to eom bine the feattire of d isulfi de bond s an d am Phi Phi lic P o l卿 erie p r o d r u g s . hi thi s researc h ， w e P reP ared 6 一m ercaP t0 Pu rin e一earb o x 扣rneth yl ehitosazis (6 一M P 一C M C ) 俪 山 diffe reni eonieni o f 6一M P w ith the aid o f a het erob ifun etion al eross一11nk er N 一suc e而 m idy l一3 一(2一P 州 dy ld ithio ) P roP io n ate (S P D P ). D isulfide b ond s w hieh we re in trod uced inio 6一M P 一C M C in order to resP on d to the m tracellular high er G S H le v e ls . 6 一M P 一C M C 、vas st ab le i n t he m e d ia e o n ia in ln g 而 c r o m o la r G S H (sim u lated P lasma con d itio ns) b ut eou ld fi巧t release 6 一M P at 而 1llm o lar G S H lev els (sim ulate d in 位a eellular eo nd itions ). Al so ，6 一M P 一C M C ean form self-assem b led nan oP 别rtlcles in P h o sPh ate bu fl七r so luti o n (PH 7 .4 ). T h e nan oP art icles ean m ain taln t h e s廿u c tu r e i n t h e m e d ia e o n t ai n in g 而 e r o m o la r G S H ，b u t d isa s se m b le a t 1 111 11油 o la r G S H le v e ls . T h e m a in c o n te n ts a n d c o n e lu s io n s o f st od y a re a s f o