本文選題：腙鍵　切入點(diǎn)：聚合物膠束　出處：《河南大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：本文設(shè)計(jì)合成了一系列主鏈含腙鍵的聚乙二醇-聚己內(nèi)酯兩親性嵌段共聚物mPEGHydPCL (AB型)與mPEGHyd(PCL)2(AB2型)。以此制備可生物降解的pH敏感聚合物膠束。從粒徑,形貌,臨界膠束濃度(CMC),載藥量以及體外釋藥等方面,考察聚合物膠束的性質(zhì)。主要研究內(nèi)容如下： (1)以含腙鍵的聚乙二醇大分子mPEGHyd, mPEGHyd-2做引發(fā)劑,通過開環(huán)聚合的方法合成一系列主鏈含腙鍵mPEGHydPCL (AB型),mPEGHyd(PCL)2(AB2型)的嵌段共聚物。采用IR、1H-NMR以及凝膠滲透色譜(GPC)對聚合物的結(jié)構(gòu)與組成進(jìn)行表征。 (2)采用自乳化溶劑蒸發(fā)法制備空白膠束與載藥膠束。應(yīng)用透射電子顯微鏡(TEM)觀察膠束的形貌,發(fā)現(xiàn)聚合物膠束呈球形具有核殼結(jié)構(gòu),分布均一。采用動態(tài)光散射法(DLS)測定膠束的粒徑及分布,實(shí)驗(yàn)表明,膠束粒徑較小,分布較窄。采用芘熒光探針法測定聚合物膠束的臨界膠束濃度(CMC),結(jié)果表明聚合物的分子結(jié)構(gòu)與分子量對臨界膠束濃度有影響,測得CMC值均小于6.03×10-4mg/mL。采用高效液相色譜(HPLC)法測定聚合物膠束的載藥量,結(jié)果顯示不同分子結(jié)構(gòu)以及不同分子量的聚合物膠束的載藥量存在差異。以紫杉醇(PTX)為模型藥物,考察了載藥膠束的體外釋放行為。實(shí)驗(yàn)結(jié)果表明,含腙鍵聚合物膠束的體外藥物釋放具有pH依賴性。藥物的釋放速度隨釋放介質(zhì)pH值的降低而加快。 (3)采用MTT法考察分析聚合物膠束的細(xì)胞毒性以及評價載藥膠束對腫瘤細(xì)胞的抑制效果。實(shí)驗(yàn)結(jié)果顯示,空白聚合物膠束對細(xì)胞幾乎沒有毒性。含腙鍵載藥聚合物膠束對人肺腺癌細(xì)胞A549的抑制作用強(qiáng)于不含腙鍵的載藥聚合物膠束。
[Abstract]:A series of poly (ethylene glycol / poly (caprolactone) amphiphilic block copolymers mPEGHydPCL AB type and mPEGHyd(PCL)2(AB2 type) with main chain Hydrazone bonds were designed and synthesized to prepare biodegradable pH sensitive polymer micelles. The properties of polymer micelles were investigated in the aspects of critical micelle concentration (CMC), drug loading and drug release in vitro. The main contents of this study were as follows:. MPEGHyd-2, a macromolecule of polyethylene glycol containing Hydrazone bond, was used as initiator. A series of block copolymers containing mPEGHydPCL (AB) type of Hydronic acid (mPEGHydPCL) were synthesized by ring-opening polymerization. The structure and composition of the polymers were characterized by IR 1H-NMR and gel permeation chromatography (GPC). (2) the blank micelles and drug-loaded micelles were prepared by the self-emulsifying solvent evaporation method. The morphology of the micelles was observed by transmission electron microscope (TEM). It was found that the polymer micelles were spherical and had core-shell structure. The particle size and distribution of micelles were measured by dynamic light scattering (DLSs). The experimental results showed that the particle size of micelles was small. The critical micelle concentration of polymer micelles was determined by pyrene fluorescence probe method. The results showed that the molecular structure and molecular weight of the polymer had an effect on the critical micelle concentration. The CMC values were less than 6.03 脳 10 ~ (-4) mg 路mL ~ (-1). High performance liquid chromatography (HPLC) was used to determine the drug loading of polymer micelles. The results showed that there were differences among different molecular structures and molecular weight of polymer micelles. The release behavior of drug-loaded micelles in vitro was investigated. The results showed that the drug release of the polymer micelles containing Hydrazone bond was pH dependent, and the release rate of the drug increased with the decrease of pH value of the release medium. The cytotoxicity of polymer micelles and the inhibitory effect of drug loaded micelles on tumor cells were investigated by MTT. Blank polymer micelles had almost no toxicity to cells. The inhibitory effect of Hydrazone conjugated polymer micelles on human lung adenocarcinoma cell line A549 was stronger than that of drug-carrying polymer micelles without Hydrazone bond.
【學(xué)位授予單位】：河南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R943

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本文編號：1568761