本文關(guān)鍵詞： 聚己內(nèi)酯 羥乙基丙烯酰胺 原子轉(zhuǎn)移自由基聚合 自組裝 膠束　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：兩親性嵌段共聚物結(jié)構(gòu)具有特殊性和多樣性,可在選擇性溶劑中自組裝成為不同形貌的納米粒子,在生物醫(yī)藥、催化等領(lǐng)域有潛在的應(yīng)用價(jià)值。近年來(lái),具有生物降解性、生物相容性、環(huán)境響應(yīng)性的膠束一直是新型功能性高分子研究的熱點(diǎn)。相比小分子,共聚物自組裝后的膠束更加穩(wěn)定,穩(wěn)定的載藥膠束能延長(zhǎng)藥物在機(jī)體內(nèi)的循環(huán)時(shí)間,有利于藥物的輸送和釋放,因此合成特定結(jié)構(gòu)的兩親性嵌段共聚物有利于獲得結(jié)構(gòu)穩(wěn)定、粒徑合適的膠束聚集體。本文通過(guò)原子轉(zhuǎn)移自由基聚合法(ATRP)合成了一種新穎的兩親性嵌段共聚物,研究了共聚物在水溶液中的膠束化行為,并考察了其載藥和釋藥性能。主要研究結(jié)果如下:通過(guò)原子轉(zhuǎn)移自由基聚合法合成了PCL-b-PHEAA兩親性嵌段共聚物。首先將聚己內(nèi)酯(PCL)和2-溴異丁酰溴(BIBB)反應(yīng),在其鏈端引入溴原子得到引發(fā)劑PCL-Br;然后利用PCL-Br引發(fā)羥乙基丙烯酰胺(HEAA)聚合,得到兩親性嵌段共聚物PCL-b-PHEAA。采用核磁共振(1H-NMR)、紅外光譜(IR)、凝膠滲透色譜儀(GPC)表征了引發(fā)劑和共聚物的化學(xué)結(jié)構(gòu)、分子量,差示掃描量熱儀(DSC)和熱重分析儀(TG)表征了共聚物的熱性能。引發(fā)劑為多孔疏松結(jié)構(gòu),嵌段共聚物為致密的層狀結(jié)構(gòu)。共聚物在50°C附近熔融,相比于PCL,共聚物分為兩個(gè)失重階段,熱穩(wěn)定性有所下降。共聚物通過(guò)透析法在水溶液中自組裝,形成球形膠束。利用熒光光譜法、激光粒度儀分別對(duì)其臨界膠束濃度(CMC)、粒徑大小及其分布進(jìn)行測(cè)定;靜滴接觸角測(cè)量?jī)x研究了親水性能;掃描電子顯微鏡(SEM)、透射電子顯微鏡(TEM)觀察膠束的形貌;另外研究了不同pH值對(duì)粒徑和形貌的影響。結(jié)果表明:共聚物通過(guò)透析法在水溶液中自組裝成穩(wěn)定的膠束體系,有明顯的丁達(dá)爾現(xiàn)象。PCL的接觸角為56.5°,共聚物溶液的接觸角在26~31°,在pH=6.8時(shí)共聚物溶液的接觸角較小。激光粒度儀測(cè)試結(jié)果表明,膠束尺寸呈單峰分布,PCL109-b-PHEAA14共聚物膠束在水溶液中的平均粒徑為490 nm,分散性良好。pH從4.0增加至9.2,膠束的粒徑減小,多分散指數(shù)變化不大。0.1 mg/mL溶液濃度制得的膠束在SEM下觀察為球形,分散性較好。酸性條件下,膠束在結(jié)晶的驅(qū)動(dòng)下有從球形轉(zhuǎn)變成棒狀或者片狀的趨勢(shì)。透射電鏡測(cè)試表明,球形膠束的平均直徑為104 nm。嵌段共聚物PCL109-b-PHEAA32的臨界膠束濃度為1.62μg/mL,PCL109-b-PHEAA14的臨界膠束濃度為12.2μg/mL。載藥膠束冷凍干燥后,SEM觀察顯示為球形,平均粒徑為564 nm。載藥膠束溶液靜置半個(gè)月后,穩(wěn)定性有所降低,粒徑明顯增加,多分散指數(shù)增加。載藥膠束的釋放行為研究表明,緩沖液中的釋放量隨著時(shí)間的延長(zhǎng)逐漸增加,后趨于平緩。這種具有生物相容性、可生物降解性的兩親性嵌段共聚物在生物醫(yī)藥領(lǐng)域有潛在的應(yīng)用價(jià)值。
[Abstract]:Amphiphilic block copolymers have special and diverse structures, which can self-assemble into nanoparticles with different morphologies in selective solvents, and have potential applications in biomedicine, catalysis, etc. In recent years, amphiphilic block copolymers are biodegradable. Biocompatibility and environmental responsiveness of micelles have been a hot topic in the study of novel functional polymers. Compared with small molecules, the micelles after self-assembly of copolymers are more stable, and stable micelles can prolong the circulation time of drugs in the body. Thus, the synthesis of amphiphilic block copolymers with specific structures is conducive to structural stability. A novel amphiphilic block copolymer was synthesized by atom transfer radical polymerization (ATRP). The micellization behavior of the copolymer in aqueous solution was studied. The main results are as follows: the amphiphilic block copolymers of PCL-b-PHEAA were synthesized by atom transfer radical polymerization. The initiator PCL-Brand the hydroxyethyl acrylamide (HEAA) polymerization initiated by PCL-Br was obtained by introducing bromine atoms into the chain end. The amphiphilic block copolymer PCL-b-PHEAA was obtained. The chemical structure and molecular weight of the initiator and copolymer were characterized by 1H-NMR-NMR, IR and GPC. The thermal properties of the copolymers were characterized by differential scanning calorimeter (DSC) and thermogravimetric analyzer (TG). The initiator was porous and the block copolymers were dense layered structures. The copolymers melted at about 50 擄C. compared with PCLs, the copolymers were divided into two weightlessness stages. The copolymers were self-assembled in aqueous solution by dialysis method to form spherical micelles. The critical micelle concentration (CMC), particle size and its distribution were measured by fluorescence spectroscopy and laser particle size analyzer. The hydrophilicity was studied by the contact angle measuring instrument, and the morphology of the micelles was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). In addition, the effects of different pH values on particle size and morphology were studied. The results showed that the copolymers were self-assembled in aqueous solution to form stable micelles by dialysis. The contact angle of the copolymers solution is 2631 擄and the contact angle of the copolymers solution is 2631 擄. The contact angle of the copolymers solution is smaller at pH=6.8. The results of laser particle size analyzer show that the contact angle of the copolymers is 56.5 擄. The average particle size of PCL109-b-PHEAA14 copolymer micelles in aqueous solution was 490nm, the dispersion of the micelles was increased from 4.0 to 9.2, the particle size of the micelles decreased, and the polydispersity index was not changed. The micelles prepared by the concentration of 0.1 mg/mL solution were spherical under SEM. The dispersibility is good. Under acidic condition, the micelle changes from spherical to rod or flake driven by crystallization. Transmission electron microscopy (TEM) test shows that, The average diameter of spherical micelles is 104nm.The critical micelle concentration of block copolymer PCL109-b-PHEAA32 is 1.62 渭 g / mLP109-b-PHEAA14, and the critical micelle concentration of PCL109-b-PHEAA14 is 12.2 渭 g / mL. The release behavior of the drug-loaded micelles increased gradually with the prolonging of time, and then tended to be gentle, which had biocompatibility, the stability decreased, the particle size increased obviously, and the polydispersity index increased, and the release behavior of the drug-loaded micelles increased gradually with the prolongation of time. Biodegradable amphiphilic block copolymers have potential applications in biomedicine.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O631;TQ460.1

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本文編號(hào)：1545779