O-季铵化改性壳聚糖固载环糊精的制备及其载药性能

对壳聚糖进行O-季铵化改性,并与羧甲基-β-环糊精在均相条件下进行缩合反应,制得O-季铵化壳聚糖固载环糊精(QCSCD),用FTIR、EA和SEM对产物进行表征。以酮洛芬为模型药物,研究其载药及药物释放行为。结果表明,季铵盐基团的引入提高了QCSCD的载药量,为3.97mg/mg,并且改变了QCSCD的pH响应性能。与壳聚糖固载环糊精相反,QCSCD在模拟胃液中的释放速率很快,而在模拟肠液中具有缓释性能。     

糠醛改性O-季铵化壳聚糖衍生物的合成及其抗菌性能

在制备水溶性较好的O-季铵化壳聚糖基础上,进一步与糠醛反应制备O-季铵化-N-呋喃亚甲基壳聚糖席夫碱及还原产物O-季铵化-N-呋喃亚甲基壳聚糖衍生物,用FTIR、1H NMR、EA（元素分析）、TG（热重分析）对产物进行表征。测定产物的最低抑菌浓度和抑菌率,并与O-季铵化-N-苯亚甲基壳聚糖席夫碱的抑菌效果进行比较。结果表明,产物对革兰氏阳性菌S.aureus的抗菌效果优于革兰氏阴性菌E. coli,在pH值5.5的条件下抗菌效果优于pH 值7.2。并且O-季铵化-N-呋喃亚甲基壳聚糖的抗菌效果>O-季铵化-N-呋喃亚甲基壳聚糖席夫碱>O-季铵化-N-苯亚甲基壳聚糖席夫碱 > O-季铵化-壳聚糖。研究表明,含呋喃杂环的壳聚糖衍生物的抗菌活性明显优于不含杂环的壳聚糖衍生物。     

季铵化两亲性壳聚糖衍生物载药性质研究

合成新型季铵化两亲性壳聚糖衍生物(DEAE-CMC)。用乳化交联固化法制备DEAE-CMC/VB12载药微球。用激光粒径仪、扫描电镜对微球的大小和形态进行表征。载药微球的平均粒径为4.53μm。在pH=7.4磷酸盐缓冲溶液中,DEAE-CMC/VB12载药微球体外药物释放达到平衡时间为60 h,药物包封率为33.70%,载药量为12.47%,平衡时药物累积释放率为56.30%。     

O-季铵化-N,N-双烷基壳聚糖的单分子膜性质研究

采用自制的季铵化试剂环氧丙基乙基三甲基氯化铵醚,制备3个不同烷基化长度的O-季铵化-N,N-双烷基壳聚糖（QADCS）,用FTIR、EA和1H NMR对产物进行表征,并试验其单分子膜性质。结果表明,所制得的QADCS可以形成稳定的单分子膜,并且QADCS单分子膜的崩溃压、极限分子面积及最大压缩模量随着侧链长度的增长而增大,其中O-季铵化-N,N-双十二烷基壳聚糖单分子膜的凝聚力最强。为进一步研究QADCS的自组装性质及载药性能提供依据。     

pH响应性的虾青素壳聚糖微球制备及应用

以氯乙酸和壳聚糖为原料，通过N,O-羧甲基化化学改性方法制备了水溶性羧甲基壳聚糖，并以此为原料通过乳液法制备羧甲基壳聚糖微球和羧甲基壳聚糖负载虾青素微球。考察了羧甲基壳聚糖微球的形态、分散性和粒径。结果表明，微球最佳制备条件为：羧甲基壳聚糖含量（以水相即去离子水质量为基准，下同）1.0%，油水体积比1∶1，表面活性剂Span 80含量（以油相即液体石蜡体积为基准，下同）4.0%，交联剂戊二醛含量（以油相即液体石蜡体积为基准，下同）7.5%，剪切速率4000 r/min。红外测试表明，微球成功负载虾青素，在虾青素初始添加量为20mg的载药率和包封率分别为10.74%和67.24%。在模拟胃液和模拟肠液中，负载虾青素微球的释放率分别为10%和85%。羧甲基壳聚糖可以用作药物载体。     

叶酸偶联N-季铵化壳聚糖的制备及其基因载体性能

首先对壳聚糖进行季铵化改性合成N-季铵化壳聚糖（HTCC）,再接枝叶酸基团制备了叶酸偶联N-季铵化壳聚糖（FA-HTCC）,用FTIR和1H NMR等对产物进行表征,并对其作为基因载体进行研究。结果表明,合成产物具有较好的水溶性,N/P为4的FA-HTCC/DNA复合物粒径为188 nm、Zeta电位为15.4 mV。与PEI和阳离子脂质体相比,FA-HTCC具有更低的细胞毒性和更高的转染效率。     

毒死蜱/壳聚糖改性凹凸棒土/海藻酸钠微球的制备与缓释性能

采用接枝方法制备了壳聚糖改性凹凸棒土,利用外源挤出法制备了毒死蜱/壳聚糖改性凹凸棒土/海藻酸钠复合微球,利用红外、热重分析和X射线衍射对改性凹凸棒土的结构进行了表征,并研究了改性凹凸棒土对载药微球的载药率、包封率、溶胀性能及缓释性能的影响。结果表明,毒死蜱仍以结晶态存在于复合微球中;壳聚糖改性凹凸棒土复合微球的载药量和包封率均高于相应的酸化凹凸棒土复合微球;加入凹凸棒土降低了载药微球的溶胀率、提高了微球的缓释性能,且壳聚糖改性凹凸棒土在抑制微球溶胀和增强缓释方面优于酸化凹凸棒土;载药微球的释药行为可用HIGUCHI动力学模型来描述。     

季铵化/磺化壳聚糖的制备及其抗生物被膜活性

合成了N-(2-羟丙基-3-甲基氯化铵)壳聚糖（HTCC）、N,N,N-三甲基壳聚糖（TMC）和N-(2-羟丙基磺酸钠)壳聚糖（HSCS）。采用红外光谱、核磁共振氢谱、元素分析对产物的结构进行表征，分别比较不同结构的壳聚糖季铵盐（HTCC和TMC）以及相似结构的壳聚糖季铵盐和壳聚糖磺酸盐（HTCC和HSCS）的抗菌活性和抗生物被膜活性。实验结果发现，将壳聚糖的氨基直接季铵化得到的壳聚糖季铵盐（TMC）的抑菌率和生物被膜清除率要优于接枝季铵化得到的壳聚糖季铵盐（HTCC），季铵化壳聚糖（HTCC）的抗菌活性和抗生物被膜活性要优于磺化壳聚糖（HSCS）。0.5mg/mL的TMC对E. coli和S. aureus的抑菌率分别为93.0%和100%。TMC在1/2MIC浓度时对E. coli和S. aureus的生物被膜形成抑制率分别为51.4%和41.5%。2.5mg/mL的TMC、HTCC和HSCS对E. coli的生物被膜去除率分别为49.1%、48.6%和21.2%，对S. aureus的生物被膜的去除率分别为85.1%、82.7%和81.8%。     

壳聚糖-明胶载药微球的制备及释放性能

以壳聚糖（Cs）和明胶（Gel）为原料,采用乳液凝聚法制备了对药物具有缓释作用的微球。以异喹啉为模拟药物,分别通过丙酮浸泡载药／常温干燥法和盐酸浸泡载药／氢氧化钠再生／冷冻干燥法,制得不同载药量的微球,并对其包封率和释放行为进行了研究。结果表明,当戊二醛（GD）与壳聚糖（Cs）的质量比为0．40～0．53,载药量在20％～30％（质量分数）之间时,壳聚糖-明胶载药微球15h后释放75％左右,包封率可以达到40％～50％,为将壳聚糖。明胶共混微球应用于生物医学领域提供了试验基础。     

甲壳素衍生物的制备工艺

介绍了多种甲壳素衍生物的制备工艺和生产方法,包括壳聚糖、羧甲基甲壳素、羧甲基壳聚糖、乙酰化壳聚糖、羧丙（乙）基壳聚糖、微晶甲壳素及壳聚塘、盐酸氨基葡萄糖、甲壳素硫酸盐、溴化甲壳素、N-乙基壳聚糖、季铵化壳聚糖、壳聚糖接枝共聚产物等十多种。     

Effect of proteolytic enzymes in gastrointestinal fluids on drug release from polyelectrolyte complex microspheres based on partially phosphorylated chitosan

This study investigated the effect of proteolytic enzymes on in vitro release of ibuprofen from phosphorylated chitosan (PCS) microspheres in simulated gastric fluid (SGF) (pH 1.4) and simulated intestinal fluid (SIF) (pH 7.4). To reduce the enzymatic degradability and to enhance the sustained release property, polyelectrolyte complex microspheres based on PCS were developed and characterized. The ibuprofen release from PCS microspheres was found to be sustained more effectively than that from CS microspheres in the medium containing proteolytic enzymes. It was concluded that the PCS microspheres can be used more successfully as sustained oral drug‐delivery vehicles than CS microspheres due to their lesser enzymatic degradability. Copyright © 2004 Society of Chemical Industry     

PEGylated chitosan microspheres as mucoadhesive drug‐delivery carriers for puerarin

PEGylated chitosans with different degrees of grafting were synthesized, and the application potential of microspheres based on PEGylated chitosan as mucoadhesive drug‐delivery carriers for puerarin was investigated. Compared with chitosan microspheres, PEGylated chitosan microspheres (PCMs) exhibited better physical stability and higher swelling capacity, and the amount of water uptake increased as the content of poly(ethylene glycol) methyl ether in the microspheres increased. PCMs showed obviously improved mucoadhesive behavior on a mucosa‐like surface. Puerarin was incorporated into the microspheres, and the release experiments in vitro showed that the PEGylation of chitosan accelerated puerarin release from the particles and decreased the retention of the drug. The abilities of all of the tested microspheres to open tight junctions and improve the permeability of puerarin were demonstrated with a Caco‐2 cell monolayer as an in vitro model. The amount of puerarin permeating across the Caco‐2 cell monolayer was significantly increased by the incorporation of puerarin into the PCMs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42623.     

Preparation and release kinetics of carboxymethyl chitosan/cellulose acetate microspheres as drug delivery system

Carboxymethyl chitosan, a water soluble chitosan derivative, was prepared from chitosan using monochloroacetic acid. Carboxymethyl chitosan/cellulose acetate microspheres (CCM) were prepared using the method of W/O/W and emulsification solvent evaporation as drug delivery system. The CCMs prepared were spherical, free‐flowing, and nonaggregated with the smooth appearance and many small pores on the surface. All CCMs prepared had sustained release efficiency for acetaminophen and the optimal formulation was that carboxymethyl chitosan of 2.0% and 1360 KD. In addition, the release rate of drug from CCMs in dilute hydrochloric acid was much slower than that in phosphate buffer saline (pH 6.8) during 24 h. It is illustrated that the drug loaded in CCMs released slower in simulated gastric fluid than that in simulated intestinal fluid. Furthermore, the drug release data showed better fitness with the first order model which indicated that the drug release from CCMs was depended on the drug concentration in the polymeric networks. And the release of drug from CCMs indicated diffusion‐controlled drug release based on Fickian diffusion and accompanied with anomalous transport (i.e., non‐Fickian diffusion) according to the values obtained from Higuchi model and Peppas models. So it was shown that the CCMs might be an ideal sustained release system for acid‐labile drugs both for the solubility of carboxymethyl chitosan and the release media. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42152.     

Human serum albumin (HSA) adsorption with chitosan microspheres

In this study, chitosan microspheres were prepared and characterized for adsorption of human serum albumin (HSA) as affinity sorbent. The chitosan microspheres were obtained with a “suspension crosslinking technique” in the size range of 30–700 μm by using a crosslinker, i.e., glutaraldehyde. The chitosan microspheres used in HSA adsorption studies were having the average size of 170 ± 81 μm. Adsorption medium pH and the initial HSA concentration in the adsorption medium were changed as 4.0–7.0 and 0.5–2.0 mg HSA/mL, respectively, to investigate the HSA adsorption capacity of chitosan microspheres. Maximum HSA adsorption (i.e., 11.35 mg HSA/g chitosan microspheres) was obtained at pH 5.0 and 1.5 mg HSA/mL of the initial HSA concentration in the adsorption medium was obtained as the saturation value for HSA adsorption. A very common dye ligand, i.e., Cibacron Blue F3GA was attached to the chitosan microspheres to increase the HSA adsorption capacity. Actually, the HSA adsorption capacity was increased up to 15.35 mg HSA/g chitosan microspheres in the case of Cibacron Blue F3GA attached to chitosan microspheres used. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3035–3039, 2002     

羟丙基壳聚糖包覆胰岛素微球的性能研究

以壳聚糖和环氧丙烷为原料合成了羟丙基壳聚糖,并以此为壳材,以胰岛素为芯材,制备了平均粒径为13．34μm的微球,并考察了微球的各种性能。通过红外光谱表征了羟丙基壳聚糖和微球的化学结构;热重分析考察了羟丙基壳聚糖微球和包覆胰岛素后微球的热稳定性;采用光学显微镜和扫描电镜观察了不同液体中微球和干品微球的形貌;采用紫外分光光度计绘制胰岛素标准曲线和测定微球的包埋率;并对微球室温下、模拟胃液和模拟肠液中进行了微球稳定性考察。所制备的微球表面光滑、致密、平均粒径适中,且分布较窄,收率和包埋率较高,室温下稳定。根据稳定性考察得出,微球有缓释的功效。     

双乳化-凝胶法制备单分散海藻酸钙微球及其载BSA研究

采用双乳化-凝胶法制备了单分散的海藻酸钙凝胶微球,并通过正交试验系统考察了海藻酸钠浓度、氯化钙浓度、表面活性剂浓度、搅拌速度和油水比对海藻酸钙凝胶微球粒径及形貌的影响。在优化的条件下,制备出了平均粒径为4μm、单分散和球形度好的海藻酸钙凝胶微球。包埋模型药物牛血清白蛋白(BSA)的过程中,以去离子水作为洗涤液洗涤海藻酸钙微球时,BSA的包封率仅为13%左右;当水洗液的pH值为3.2时,BSA的包封率提高到66%左右,载药率可达16%,这是海藻酸钙pH值响应溶胀和BSA与海藻酸盐之间静电作用的结果。微球中BSA的体外释放曲线表明,该系统具有在模拟胃液中释药速率慢、释药量低、模拟肠液中释药迅速的特性。因此,双乳化-凝胶法制备海藻酸钙微球有望成为制备蛋白类药物控释制剂的一种新方法,以达到靶向快速给药的目的。     

Preparation of surface‐modified,micrometer‐sized carboxymethyl chitosan drug‐loaded microspheres

Drug‐loaded microspheres have attracted much attention in embolization therapy for liver cancer in recent years. Carboxymethyl chitosan has obvious advantages for biomedical applications because of its exceptional biocompatibility and biodegradability. In this study, surface‐modified carboxymethyl chitosan microspheres were prepared by the crosslinking reactions of carboxymethyl chitosan in a reverse suspension system with poly(ethylene glycol diglycidyl ether) (PEGDE) as the crosslinking agent; this was followed by the grafting polymerization of 2‐acrylamido‐2‐methyl propane sulfonic acid on the surface of the microspheres. The microspheres showed regular spherical shapes with size distributions ranging from 300 to 600 μm. Ion‐exchange groups (? COOH, ? SO₃H) were introduced into the microspheres; these groups could load doxorubicin with a loading rate as high as 34.6% in 24 h. This was an increase of 49.8% compared to that of the pure carboxymethyl chitosan microspheres. Additionally, the microspheres possessed large network structures because macromolecular PEGDE was used as the crosslinking agent. The drug‐release profile showed that the surface‐modified microspheres displayed a sustained‐release manner compared with the nonmodified microspheres in phosphate‐buffered saline. These microspheres have promising applications as drug‐loaded arterial embolization agents for the interventional treatment of tumors. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45731.     

Preparation of porous chitosan/agarose microsphere and its R‐phycoerythrin release properties

The chitosan microspheres (CS‐CL) were prepared by suspension crosslinking method and used as carriers of R‐phycoerythrin (R‐PE). In this study, R‐PE was loaded in the microspheres and released in vitro. The effects of pH value, temperature, ionic strength, and R‐PE concentration on loading efficiency and release behavior were discussed. A novel microsphere that contained agarose (CS‐AR MP) was prepared and the basic loading and releasing behavior for R‐PE of this kind of new microspheres were also investigated. The results showed that all these chitosan microspheres have the ability to control‐release R‐PE. The addition of agarose may somewhat accelerate the release rate of R‐PE from microspheres and reduce the capacity of adsorption for R‐PE. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2759–2766, 2007     

“类乒乓球”状壳聚糖微球对环丙沙星的控制释放性能的研究

以甲醛作为交联剂,通过悬浮交联法得到单分散性的微米级微球。采用分光光度法研究了壳聚糖微球对环丙沙星的载药释药性能,考察了环丙沙星初始浓度、pH、微球粒径大小、载药时间及温度对饱和吸附量的影响。结果表明,在初始浓度为200 mg/L,pH为8.80和时间为65 min,温度为37℃的优化条件下,壳聚糖微球对环丙沙星的载药量最大,最大吸附量为325 mg/g。在pH为7.4,温度为37℃的模拟人体肠胃缓冲溶液(NaH2PO4/NaOH)中研究了初始浓度以及释放时间对释放结果的影响。实验表明,环丙沙星在担载时与环丙沙星的初始浓度有关,浓度越大,担载量越大,但是担载效率和浓度之间无确定的线性关系。在环丙沙星释放初期有明显的释放现象,但是随着时间的推移,药物释放逐渐稳定,释药效率可达97%左右。