第一篇：殼聚糖論文：新型環(huán)糊精固載殼聚糖的合成及其納米給藥系統(tǒng)的研究

殼聚糖論文：新型β-環(huán)糊精固載殼聚糖的合成及其納米給藥系統(tǒng)的研究

【中文摘要】p-環(huán)糊精(p-CD)和殼聚糖(CS)都是生物相容性好、可降解的大然高分子材料,已被廣泛的應(yīng)用與藥物傳遞等領(lǐng)域。本課題是新型β-環(huán)糊精固載殼聚糖(CD-g-NMCS)的合成及其納米給藥系統(tǒng)的研究。首先將p-CD與對(duì)甲苯磺酰氯反應(yīng)得到活化的p-CD衍生物(6-OTs-β-CD),與CS反應(yīng)得到了一系列不同環(huán)糊精取代度(DSCD=0～22.86%)的β-環(huán)糊精固載殼聚糖(CD-g-CS),使用1hNMR, IR,XRD手段表征其結(jié)構(gòu),采用硫酸-苯酚法測(cè)定CD-g-CS的DSCD,通過(guò)正交實(shí)驗(yàn)優(yōu)化了CD-g-CS的合成條件。采用DSCD= 14.60%的CD-g-CS進(jìn)一步馬來(lái)酸酐?；?通過(guò)控制馬來(lái)酸酐與CD-g-CS的質(zhì)量比,得到一系列不同羧基取代度(DSCOOH=0～30%)的CD-g-NMCS并表征,采用電位滴定法測(cè)定CD-g-NMCS的羧基取代度(DSCOOH),考察了CD-g-NMCS新材料的水溶性、粘均分子量和細(xì)胞毒性。以CD-g-CS(DSCD= 14.60%), CD-g-NMCS20(DSCOOH= 20%)和CD-g-NMCS30(DSCOOH= 30%)為載體材料,以三聚磷酸鈉(TPP)為交聯(lián)劑采用離子凝膠法制備納米粒,考察了制備納米粒的條件,在pH=5.0, CD-g-NMCS:TPP= 10:1(w/w)時(shí)制得的納米粒徑為190-280 nm,呈球形,zeta電位為+20-+30 mV。以酮洛芬(KTP)為模型藥物,制備了三種包載KTP的CD-g-NMCS納米粒,具有較高的載藥率和包封率。在不同pH(pH=4.0,6.8和7.4)釋放介質(zhì)中考察了載藥納米粒的體外釋放特

性,實(shí)驗(yàn)結(jié)果顯示在pH 6.8和7.4的釋放介質(zhì)中納米粒具有一定的緩釋釋藥效果,CD-g-NMCS納米所用的載體材料的羧基取代度越高其載藥納米粒的體外釋藥速度越快。CD-g-NMCS納米粒體外釋藥具有pH敏感性。CD-g-NMCS在納米給藥領(lǐng)域具有潛在的應(yīng)用價(jià)值。

【英文摘要】(3-Cyclodextrin(P-CD)can form inclusion complexes with a variety of drugs, which can increase solubility, improve chemical and physical stability and/or enhance oral absorption of the drug.Chitosan(CS)is used as a bioadhesive polymer since and the CS has non-toxic, biodegradable, biocompatible.mucoadhesion.β-CD and CS have been widely used with drug delivery system.In this study, according to the advantages of both CD and CS derivative, we synthesized N-maleoyl chitosan bearing pendant cyclodextrin(CD-g-NMCS)and prepared CD-g-NMCS nanoparticles for drug delivery.In this study, the CD-g-NMCS polymer was synthesized by reacting maleic anhydride and chitosan bearing pendant cyclodextrin.which was prepared with CS and 6-OTs-β-CD, which was prepared with(3-CD and TsCl.The differentβ-CD substitute degrees(DSCD)of CD-g-CS could be obtained by adjusting mass ratio of 6-OTs-β-CD to CS, and confirmed by the 1HNMR, IR, XRD.Orthogonal experiments were used to optimize the reaction conditions.The different carboxyl substitute degrees(DSCOOH)

of CD-g-NMCS could be obtained by adjusting mass ratio of maleic anhydride to chitosan bearing pendant cyclodextrin(CD-g-CS).CD-g-NMCS was confirmed by the 1HNMR.IR.XRD.The water-solubility, viscosity average molecular weight and cell toxicity of the CD-g-NMCS were examined.CD-g-CS(DSCD= 14.60%).CD-g-NMCS20(DSCOOH= 21.2%)and CD-g-NMCS30(DSCOOH= 30.5%)nanoparticles were obtained by ionic gelation method using sodium tripolyphosphate(TPP).which possessed spherical morphology, uniform size(190～280 nm), positive electrical charge(+20～+30 mV).Entrapment drug studies of the nanoparticles were conducted using ketoprofen(KTP)as a model drug.Various influencing factors in prepartion process were studied, and the drug release tests of the nanoparticles were carried out in vitro using PBS(pH= 4.0.6.8 and 7.4).The in vitro drug release study showed that the KTP-loaded CD-g-NMCS nanoparticles have prolonged release of drug.The in vitro release study indicated CD-g-NMCS nanoparticles had controlled-release effect.The nanoparticles were pH-sensitive.The degree of drug release from KTP-loaded CD-g-NMCS nanoparticles was depended on the DS of CD-g-NMCS.These results found that CD-g-NMCS nanoparticles was a new promising vehicle for controlled release drug.【關(guān)鍵詞】殼聚糖 β-環(huán)糊精 酮洛芬 納米給藥系統(tǒng) 【備注】索購(gòu)全文在線

：139938848

....同時(shí)提供論文寫作一對(duì)一指導(dǎo)和論文發(fā)表委托服務(wù) 【英文關(guān)鍵詞】Chitosan β-Cyclodextrin Ketoprofen Nanoparticles 【目錄】新型β-環(huán)糊精固載殼聚糖的合成及其納米給藥系統(tǒng)的研究9-1812-15依據(jù)17-1818-191919摘要5-6

Abstract6

第1章 前言1.2 環(huán)糊精概述

1.4 立項(xiàng)2.1 引言1.1 殼聚糖概述9-121.3 環(huán)糊精固載殼聚糖的應(yīng)用15-17

第2章 CD-g-CS的合成18-282.2 實(shí)驗(yàn)方法19-20

2.2.1 材料與儀器2.2.2 單-6-對(duì)甲苯磺酰-β-環(huán)糊精酯的制備2.2.3 環(huán)糊精固載殼聚糖的制備19

2.2.4 CD-g-CS的表征1919-20討論20-2720-212.2.5 環(huán)糊精取代度和羧基取代度的測(cè)定方法2.2.6 CD-g-CS反應(yīng)條件的優(yōu)化20

2.3 結(jié)果與

2.3.1 單-6-對(duì)甲苯磺酰-β-環(huán)糊精酯的制備2.3.2 環(huán)糊精固載殼聚糖的制備

2121-2

42.3.3 環(huán)糊精固載殼聚糖的表征24-2525-2728-3929-30

2.3.4 環(huán)糊精取代度的測(cè)定2.3.5 環(huán)糊精固載殼聚糖合成條件的優(yōu)化2.4 小結(jié)27-283.1 引言28-29

第3章 CD-g-NMCS的合成3.2 實(shí)驗(yàn)方法

3.2.2 環(huán)糊精固載N-馬來(lái)3.2.1 材料與儀器29

?；瘹ぞ厶堑闹苽?9

293.2.3 CD-g-NMCS的表征

3.2.5 CD-g-NMCS3.2.4 羧基取代度的測(cè)定29-30反應(yīng)條件的優(yōu)化30解性能的測(cè)定3030

3.2.6 CD-g-NMCS在不同pH值水溶液中溶3.2.7 CD-g-NMCS相對(duì)分子質(zhì)量的測(cè)定

3.3 結(jié)果與討3.2.8 CD-g-NMCS細(xì)胞毒性的測(cè)定30論30-3830-313.3.1 環(huán)糊精固載N-馬來(lái)?；瘹ぞ厶堑闹苽?.3.2 CD-g-NMCS的表征31-3

33.3.3 CD-g-NMCS反應(yīng)條件的優(yōu)化33-35中溶解性能的測(cè)定35-36結(jié)38-3939-5340-42

53.3.4 CD-g-NMCS在不同pH值水溶液3.3.5 相對(duì)分子質(zhì)量的測(cè)定

3.4 小3.3.6 CD-g-NMCS細(xì)胞毒性的測(cè)定36-38第4章 CD-g-NMCS納米粒給藥系統(tǒng)的研究4.1 引言39-40

4.2 實(shí)驗(yàn)方法4.2.1 材料與儀器404.2.2 空白CD-g-NMCS納米粒的制備40性考察40-4141

4.2.3 空白CD-g-NMCS納米粒在PBS中的穩(wěn)定4.2.4 包載酮洛芬的CD-g-NMCS納米粒的制備

4.2.6 4.3 結(jié)果4.2.5 載藥納米粒包封率、載藥率的測(cè)定41包載酮洛芬的CD-g-NMCS納米粒的體外釋放41-42與討論42-5242-4343-4444-4646-52

4.3.1 空白CD-g-NMCS納米粒的制備與表征4.3.2 空白CD-g-NMCS納米粒在PBS中的降解4.3.3 包載酮洛芬的CD-g-NMCS納米粒的制備與表征4.3.4 包載酮洛芬的CD-g-NMCS納米粒的釋藥特性4.4 小結(jié)52-53

全文結(jié)論53-54

參考文

獻(xiàn)54-5966-67寫詞68-69綜述59-66參考文獻(xiàn)65-66致謝附錄2 縮附錄1 碩士期間發(fā)表論文情況67-68

卷內(nèi)備考表69