壳聚糖载药微囊的制备及应用研究进展

壳聚糖是一种具有优良的生物降解性、生物相容性和生物黏附性的天然高分子材料，本文对壳聚糖载药微囊的制备方法：乳化一交联法、离子凝胶法、自凝聚法以及壳聚糖微囊作为药物载体的应用进行了综述。     

疏水修饰磁性壳聚糖载药纳米粒子的制备与表征

利用O-羧甲基壳聚糖(O-CMC)的表面多种官能团(如-NH_2,-OH,-COOH等)与胆酸(CA)进行化学修饰得到两亲性共聚物,再以反溶剂法将Fe_3O_4和阿霉素(DOX)包埋在两亲性共聚物疏水的核中,制备两亲性的磁性壳聚糖载药纳米粒子,并对磁性载药纳米粒子的形貌、粒径大小、磁性、药物控释等进行了研究。结果表明:磁性壳聚糖纳米粒子有较高的药物包埋效率(92.3%),与自由阿霉素相比,磁性复合物具有明显的缓释作用和pH响应性;同时,有较好的超顺磁性。这些说明制备的疏水修饰磁性壳聚糖载药纳米粒子具有双重响应性,有望作为药物输送载体对肿瘤进行实时跟踪、诊断和治疗。     

水溶性壳聚糖纳米粒子的制备及其BSA载药性能

为了避免高分子量壳聚糖水溶性差以及增溶剂乙酸可能带来的负面作用,本文选择低分子量水溶性壳聚糖 (WSC)作研究对象,采用三聚磷酸(TPP)作交链剂制备不同WSC/TPP比率的WSC纳米粒子,并用于牛血清白蛋白 (BSA)的释放载体。经测得为球形形貌的纳米粒子空载和载药时粒径、Zeta电位分别在35～190 nm、35～42 mV。红外光谱及X–射线衍射证实了纳米粒子中WSC的氨基与TPP的磷酸基团发生了交联反应。纳米粒子载药性能试验表明在0.05～1 mg/mL范围内随着BSA浓度的增大,纳米粒子的载药量增加而负载率降低。体外释放实验表明水溶性壳聚糖纳米载体对蛋白质药物具有缓释特征。因此,水溶性壳聚糖有望成为新的载体应用于蛋白质药物的控制释放。     

超声诊疗一体化的载药壳聚糖纳米微泡的制备

载药微泡在超声诊疗一体化中具有广阔的应用前景。以壳聚糖为原料制备了一种能够实现超声诊疗一体化功能的载药壳聚糖纳米微泡,采用激光粒度仪、透射电镜、扫描电镜、紫外分光光度计、超声成像仪以及圆二色谱仪等对载药纳米微泡进行表征,研究了载药纳米微泡的稳定性,并验证了其体外超声显影和超声释放的能力。结果表明,载药纳米微泡平均粒径为(136.54±4.46) nm,粒径均一且分散性好,药物的包封率和载药率分别为43.1%±1.3%和4.1%±0.01%。体外实验证实该载药纳米微泡具有的空核结构能够实现超声显影功能,且通过聚焦超声可实现对纳米微泡中包裹的药物进行体外定点释放。制备的载药纳米微泡有望在超声诊疗一体化应用中提供技术指导。     

Pickering乳液在药物载体制备方面的研究进展

Pickering乳液具有成本低、稳定性好、毒性小等优点,广泛应用于化妆品、食品、医药等方面。利用Pickering乳液制备药物载体操作简单,可改善难溶药物的溶出,对药物具有一定的缓释效果,其在药物载体方面具有广阔的发展前景。本文综述了近些年Pickering乳液在药物载体方面的研究进展,首先简要介绍了药物缓释技术及Pickering乳液性质;然后重点分析了不同固体粒子稳定的Pickering乳液在载药微球制备中的研究;还探讨了Pickering乳液在制备载药凝胶、载药多孔支架以及载药乳剂等方面的应用;最后对Pickering乳液制备药物载体方面作出展望,随着该技术相关研究的发展和成熟,药物载体的稳定性、生物相容性等问题的突破,利用Pickering乳液制备药物载体的方法技术将更有利于药物载药体系的发展。     

静电喷雾技术制备载药微／纳米粒子研究进展

静电喷雾技术是一种新型的载药微／纳米粒子制备方法。该技术可通过将药物混合或包裹于人工／天然高分子材料,形成混合型或核壳型载药微／纳米粒子,提高药物的分散性与稳定性、延长药物的作用时间、降低药物毒副作用、形成靶向性制剂。本文旨在对静电喷雾技术制备载药微／纳米粒子的基本原理及制备过程影响因素进行综述。     

pH敏感性生物基纳米载药粒子的研究进展

生物基来源的聚合物具有生物相容性高、无毒易降解等优势,近些年来作为药物载体在生物医药领域受到了广泛的关注。人体内的生理环境存在pH差异,利用pH作为刺激响应的信号,可以赋予聚合物纳米载药系统理想的靶向释药性能。本综述着眼于pH敏感性的生物基聚合物纳米粒子,揭示了纳米载药粒子中化学键断裂与质子化作用两种pH响应的控释机制,并针对两者的控释特点进行了分析总结。在此基础上,介绍了几种生物基药物载体的pH控释研究及其在生物医药领域的应用进展,并提出了目前利用各种生物基材料作为药物载体存在的问题。最后,针对目前存在的载药量低、敏感性不强等问题,提出了可采用多种方式联合载药、多重刺激响应结合等方式进行深入研究的展望。     

竹叶黄酮壳聚糖缓释微球的制备及其性能研究

以壳聚糖为载体材料,戊二醛为交联剂,竹叶黄酮作为模型药物,采用乳化交联法,制备了载竹叶黄酮壳聚糖缓释微球。研究了载药比对微球的形貌、药物收率、包埋率和载药量的影响。结果表明:竹叶黄酮-壳聚糖微球呈规则球形,粒径10~50μm;竹叶黄酮经壳聚糖加载后,其释放时间长,释药均匀,具有良好的缓释性能。     

交联壳聚糖磁性微球制备及吸附性能研究

采用超声波辅助化学共沉淀法制备纳米Fe3O4,在此基础上选用乳化交联法,以戊二醛为交联剂,壳聚糖为单体包埋磁性纳米颗粒,合成了微米及纳米尺度上具有高吸附性、介质分离的磁性壳聚糖纳米微球(MCTS),并对复合材料的吸附性能进行了讨论。通过将壳聚糖包裹纳米磁性粒子制备成的磁性壳聚糖微球,具有比表面积大、多孔、易回收、可再生等优点,并且该磁性微球稳定性好、吸附性能强,有效地提高了壳聚糖的应用价值,而对于金属废水处理、药物的分离纯化和天然药物有效成分的富集纯化等意义重大。     

静电自组装壳聚糖载药空心微胶囊的制备及释放性能

采用目前材料领域新型的自组装模板法制备了壳聚糖空心微胶囊。首先使用分散聚合的方法合成了粒径均一的聚苯乙烯微球,粒径范围在1~2μm。然后用H2SO4将聚苯乙烯表面功能化为磺化聚苯乙烯,并以之为模板,将壳聚糖静电组装于其表面,经戊二醛交联后用四氢呋喃溶解模板,成功制备出生物相容和可降解的交联壳聚糖空心微胶囊。研究采用凝胶渗透色谱和纳米粒度仪测试合成聚苯乙烯微球的分子量、粒径及粒度分布等性能;利用Zeta电位仪、扫描电镜、透射电镜和热重分析仪对核-壳结构与空心微胶囊的特性进行表征。以吡虫啉为模型药物,通过吸附与渗透的方式负载到壳聚糖交联空心微胶囊,在甲醇下进行缓释实验。傅里叶转换红外光谱仪的表征证明氢键力在壳聚糖对吡虫啉的负载起到了重要作用。释放实验的结果表明,壳聚糖空心微胶囊对吡虫啉的载药量达到31.78%,前期出现的释放量达56.63%,释放实验后期能保持一定的缓慢释放量,表明壳聚糖空心微胶囊的载药部位主要在其表面与内部,而进入微胶囊内部的药物则需要在交联壳聚糖降解后缓慢释出,达到所期望的缓释效果。     

聚氧化乙烯/海藻酸钠/羟丙基-癸烷基壳聚糖网络凝胶的制备及其对三七总皂苷的体外释放性能研究

将壳聚糖改性成两亲性的羟丙基-癸烷基壳聚糖,并通过化学交联方法制备了聚氧化乙烯/海藻酸钠/羟丙基-癸烷基壳聚糖载药网络凝胶。利用傅利叶变换红外光谱仪、X-射线衍射仪、扫描电子显微镜对凝胶结构进行了表征。实验结果表明,该凝胶具有良好的网状结构和溶胀性,同时兼具p H敏感性和温度敏感性,在不同p H环境中均对三七总皂苷具有一定的缓释作用。     

高压静电法制备载阿糖胞苷海藻酸钙-几丁聚糖微胶囊

采用海藻硅酸钠和几丁聚糖为原料制备海藻酸钙-几丁聚糖药物缓释微胶囊,初步考察了载阿糖胞苷微胶囊的制备以及不同分子量几丁聚糖、静/动态载药方式对阿糖胞苷释放性能的影响。     

Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution

Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments.     

戊二醛与甲醛交联壳聚糖微球的比较研究

壳聚糖微球是肥料和农药的重要缓释载体之一。根据相关实验数据及文献显示,纯的壳聚糖成球性能差,易溶解,需要加入一定的交联剂、乳化剂和致孔剂对其进行交联改性,改善微球的性能。分别采用戊二醛、甲醛两种交联剂,通过乳化-化学交联方法制备壳聚糖微球。通过扫描电子显微镜对壳聚糖微球表面、内部结构及形态特征进行观察,测量壳聚糖微球粒径的大小。采用红外光谱(FT-IR)以及交联度测试对两种交联微球进行了对比。结果表明:以戊二醛为交联剂所制得的壳聚糖微球各个方面性能均优于以甲醛为交联剂所制得的壳聚糖微球。     

N-mPEG-O-季铵化壳聚糖微球的制备及其载药性能

将聚乙二醇单甲醚（mPEG）醛化改性后,通过西佛碱反应接枝到自制的O-季铵化壳聚糖的NH2上,硼氢化钠还原制得N-mPEG接枝O-季铵化壳聚糖（QACS-mPEG）,反相悬浮法制备二乙烯基砜交联QACS-mPEG微球。用FTIR、1 H NMR、EA和SEM对产物进行表征,并且以酮洛芬为模型药物研究微球的载药性能及释放行为。结果表明,mPEG和季铵盐基团的引入提高了N-mPEG-O-季铵化壳聚糖微球的载药量,为4.31mg/mg;载药N-mPEG-O-季铵化壳聚糖微球在模拟肠液的缓释效果优于胃液,微球释药具有pH响应性。     

阿司匹林-壳聚糖缓释微球的制备和释药性能研究

采用乳化交联法制备阿司匹林-壳聚糖缓释凝胶微球,通过透析实验检测微球的体外释放特性。应用正交实验设计,考察了壳聚糖浓度,搅拌速度,阿司匹林/壳聚糖质量比,交联时间对微球制备的影响。体外释放实验表明,壳聚糖微球前5个小时的释放符合SRP的释药行为。以5个小时的体外释放总量为指标进行直观分析,交联时间对5小时的体外释放总量影响最大。     

壳聚糖的性能及在电化学生物传感器中的应用

壳聚糖又称脱乙酰甲壳素,是由自然界广泛存在的几丁质（chitin）经过脱乙酰作用得到的,化学名称为聚葡萄糖胺（1-4）-2-氨基-B-D葡萄糖,属带阳离子性质的碱性多糖。壳聚糖作为资源富足、作用普遍的高分子化合物,兼有生物相容性和可生物降解等特点,被广泛运用于医药、食品、化工、化妆品等领域。利用壳聚糖成膜性较好及其特有的表面基团,采用吸附法、共价交联法等方法,壳聚糖可以与其它活性材料形成复合膜作为固定基质修饰电极。本文介绍了壳聚糖的结构、物理化学性质、常见的制备方法,综述了基于壳聚糖的电化学生物传感器在医学领域、环境监测和食品安全中的应用.     

以乙二醛为交联剂的壳聚糖纤维交联机理探索

采用乙二醛为交联剂对壳聚糖纤维进行交联处理以改善纤维强度。基于对红外光谱和核磁共振图谱的分析,探索了乙二醛与壳聚糖纤维交联反应的机理。研究结果表明,乙二醛特殊的化学结构使其利于亲核试剂的攻击,而壳聚糖的氨基和羟基具有亲核性,因此乙二醛可以与壳聚糖发生交联反应。交联反应主要有两类:一类是发生在壳聚糖C2氨基与乙二醛羰基之间的Schiff碱反应,占据主导地位;另一类是发生在壳聚糖C6羟基与乙二醛羰基之间的缩醛化反应,处于次要地位。     

Effect of cross-linking method on the activity of spray-dried chitosan microparticles with immobilized laccase

The effect of processing method on the properties of cross-linked chitosan microparticles and on the enzymatic activity of laccase immobilized in the particles has been investigated. Chitosan has been cross-linked by tri-polyphosphate (TPP) using two methods – the so called ex situ cross-linking whereby the solutions of chitosan, TPP and the enzyme have been pre-mixed and spray-dried by a standard two-fluid kinetic nozzle, and a novel in situ cross-linking method, whereby the solutions have been contacted at the tip of a three-fluid nozzle and cross-linking occurred within a drying droplet. The influence of the cross-linking method on the particle size and morphology, surface charge, and swelling ratio has been determined. The enzymatic activity of laccase toward the oxidation of a chromophore substrate (ABTS) has been systematically investigated and found to be superior in particles produced by the in situ cross-linking method.     

Preparation of chitosan nanoparticles and their application to Antheraea pernyi silk

In this study, a chitosan nanoparticle dispersion solution as a novel multifunctional agent was developed to modify Antheraea pernyi silk. An ionization gelation methodology with chitosan and sodium tripolyphosphate (STPP) was used to prepare the chitosan nanoparticle solution, and then, Fourier transform infrared spectra, laser particle size analysis, and transmission electron microscopy (TEM) were used to characterize the structure and size distribution of the chitosan nanoparticles. The peaks at 3390.7, 1633.7, 1538.2, and 1258.1 cm⁻¹ revealed the reaction between the chitosan and STPP molecules in the chitosan nanoparticles. The average size of the nanoparticles in the aqueous dispersion solution was approximately 20 nm. TEM images clearly showed the round spherical morphology and the distribution of the particles in the solid state. The obtained chitosan nanoparticle dispersion solution was then applied to treat silk filaments and fabric. The results indicate that the surface of the chitosan‐nanoparticle‐treated A. pernyi silk fiber was rougher than that of the chitosan‐treated and untreated ones, and a higher specific surface was achieved. In addition, the antibacterial activity, breaking strength, and wrinkle‐resistance properties of the chitosan‐nanoparticle‐treated A. pernyi silk fabric were also enhanced. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010