基于瞬時(shí)納米沉淀法可控制備載藥納米粒子
本文關(guān)鍵詞: 瞬時(shí)納米沉淀法 載藥納米粒子 mPEG-b-PCL β-胡蘿卜素 出處:《華東理工大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:瞬時(shí)納米沉淀(Flashnanoprecipitation,FNP)技術(shù),是一種可以在極短時(shí)間內(nèi)制備包含有機(jī)活性物質(zhì)的聚合物納米粒子的新型技術(shù)。與傳統(tǒng)的透析法制備納米粒子相比,FNP技術(shù)的優(yōu)勢在于其大大縮短了納米粒子的制備時(shí)間,整個(gè)制備流程在幾秒內(nèi)即可完成。近年來利用FNP技術(shù)制備納米粒子得到了越來越多的關(guān)注。本文旨在通過兩親性嵌段共聚物甲氧基聚乙二醇-b-聚己內(nèi)酯(mPEG-b-PCL)的制備和對(duì)模型藥物β-胡蘿卜素的包裹,對(duì)利用FNP技術(shù)制備載藥納米粒子進(jìn)行進(jìn)一步的基礎(chǔ)研究。在聚合物mPEG-3-PCL中,mPEG、PCL均具有良好的生物相容性,且PCL具有很好的生物降解性,可以被廣泛運(yùn)用于載藥領(lǐng)域。本文合成了一系列具有不同分子量及不同分子結(jié)構(gòu)的兩親性嵌段聚合物,并用核磁共振氫譜、凝膠滲透色譜測定了其分子量,利用熒光分光光度計(jì)測試了其臨界膠束濃度。隨后,以β-胡蘿卜素作為模型藥物,利用FNP技術(shù)制備了一系列包裹有β-胡蘿卜素的納米粒子。通過改變兩親性共聚物的結(jié)構(gòu)、分子量、濃度及溶劑比(H20/THF)成功實(shí)現(xiàn)了對(duì)納米粒子尺寸的調(diào)控。實(shí)驗(yàn)結(jié)果表明:在實(shí)驗(yàn)研究范圍內(nèi),聚合物親水部分比例增大,納米粒子尺寸減小;親水部分比例相同時(shí),分子量越大,納米粒子尺寸越小;當(dāng)聚合物濃度較高時(shí)(1Og/L),制備的納米粒子粒徑分布更窄,粒子更穩(wěn)定。另外,本文也對(duì)利用FNP技術(shù)制備三嵌段聚合物載藥納米粒子進(jìn)行了初步探索,但是由于其穩(wěn)定性較差,其構(gòu)效關(guān)系有待進(jìn)一步深入研究。最后,本文對(duì)比了利用傳統(tǒng)的透析法與FNP技術(shù)制備載藥納米粒子,實(shí)驗(yàn)結(jié)果表明:在實(shí)驗(yàn)研究范圍內(nèi),當(dāng)聚合物相同時(shí),利用FNP技術(shù)制備得到的載藥納米粒子的包封率及載藥率均高于傳統(tǒng)法制備的納米粒子,且前者的制備時(shí)間短,效率高。通過以上研究,本文成功實(shí)現(xiàn)了利用FNP技術(shù)制備尺寸可調(diào)控二嵌段載藥聚合物納米粒子,為FNP技術(shù)的進(jìn)一步研究和應(yīng)用奠定了相關(guān)的工作基礎(chǔ)。
[Abstract]:Flashnanoprecipitation-FNPs technique for transient nanoprecipitation. It is a new technology to prepare polymer nanoparticles containing organic active substances in a very short time, compared with the traditional dialysis method. The advantage of FNP technology is that it shortens the preparation time of nanoparticles. The whole preparation process can be completed in a few seconds. In recent years, more and more attention has been paid to the preparation of nanoparticles using FNP technology. The aim of this paper is to use amphiphilic block copolymer methoxy polyethylene glycol-b-polycaprolactone. (. Preparation of mPEG-b-PCL and encapsulation of model drug 尾 -carotene. The preparation of drug loaded nanoparticles by FNP technology was further studied. All of them have good biocompatibility in polymer mPEG-3-PCL. PCL has good biodegradability and can be widely used in the field of drug loading. A series of amphiphilic block polymers with different molecular weight and molecular structure were synthesized and used in nuclear magnetic resonance spectroscopy (NMR). The molecular weight was determined by gel permeation chromatography, the critical micelle concentration was measured by fluorescence spectrophotometer, and then 尾 -carotene was used as the model drug. A series of nanoparticles coated with 尾 -carotene were prepared by FNP technique. The molecular weight of the amphiphilic copolymers was changed by changing the structure of the copolymers. The concentration and solvent ratio of H20 / THFs have successfully controlled the size of nanoparticles. The experimental results show that in the range of experimental study, the proportion of hydrophilic part of polymer increases and the size of nanoparticles decreases. When the proportion of hydrophilic part is the same, the larger the molecular weight, the smaller the size of nanoparticles. When the polymer concentration is higher, the particle size distribution is narrower and the particle size is more stable. In this paper, the preparation of triblock polymer drug-loaded nanoparticles using FNP technology was also explored, but because of its poor stability, its structure-activity relationship needs to be further studied. Finally. In this paper, the preparation of drug loaded nanoparticles by traditional dialysis method and FNP technology is compared. The experimental results show that: in the range of experimental study, when the polymer is the same. The encapsulation efficiency and drug loading rate of the drug loaded nanoparticles prepared by FNP technology are higher than those of the traditional method, and the preparation time of the former is short and the efficiency is high. In this paper, the preparation of diblock drug loaded polymer nanoparticles by FNP has been successfully realized, which lays a foundation for the further research and application of FNP technology.
【學(xué)位授予單位】:華東理工大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:TQ460.1;TB383.1
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