壳聚糖水凝胶的制备及其在药物释放中的应用

水凝胶作为性能良好的载体,在药物的控释、组织工程等领域有着广泛的应用。壳聚糖是一类天然的带正电荷的碱性多糖,由其形成的水凝胶具有较好的生物相容性、生物降解性、抗菌和低细胞毒性,因此,壳聚糖水凝胶有着良好的生物应用前景。本文综述了壳聚糖水凝胶的制备方法(包括物理交联法和化学交联法),在物理交联法部分着重介绍了离子化合物及聚电解质分子与壳聚糖通过离子交联形成水凝胶,以及利用分子链间的疏水作用形成壳聚糖水凝胶的方法;而在化学交联法部分介绍了合成壳聚糖水凝胶的化学手段,包括交联剂、光照辐射和酶的使用。继而概述了壳聚糖水凝胶在药物缓释应用方面的研究进展,包括温度、pH值和电场响应的药物控释体系。最后展望了壳聚糖水凝胶未来的发展前景。     

空心羟基磷灰石亚微球/壳聚糖可注射水凝胶的制备及表征

采用W/O/W复乳法制备空心羟基磷灰石(HAP)亚微球,将空心HAP亚微球均匀分布在壳聚糖/甘油磷酸钠(CS/GP)体系中制备可注射HAP/CS水凝胶(gel 1),同时制备可注射CS水凝胶(gel 2).用X射线衍射仪、场发射透射电镜、红外光谱、扫描电镜对空心HAP亚微球和水凝胶进行了表征,并比较分析了两种溶胶的成胶...     

纳米金刚石/酵母-壳聚糖复合微球的制备及光热控释性能

开发高性能功能性光热凝胶并建立药物控释模型对农药智能输送材料的开发具有重要意义。以酵母-壳聚糖水凝胶(YS-CS)为基体,引入光热材料纳米金刚石(DND),通过碱凝胶法合成了纳米金刚石/酵母-壳聚糖(DND/YS-CS)交联网络结构复合凝胶微球,研究了复合微球的微观结构、力学性能和光热转换性能;以吲哚丁酸(IBA)为模型药物,探讨DND/YS-CS对IBA的负载性能和控释性能,揭示复合微球对IBA的光热控释机制。结果表明：复合微球具有良好的力学性能,在分别超声和离心1 h后,DND含量为2.0 mg/mL复合微球保水能力分别达到70.5%和74%;复合微球具有良好的光热转换能力,一个太阳光强度下,最高温度可达37.6℃;DND含量为1.2 mg/mL复合微球对IBA的吸附量最高,可达到41.73μg/mg;微球在光下药物释放模式符合Korsmeyer-Peppas模型,在光下具有明显的刺激响应行为,药物释放呈现“开-关”模式。通过控制光的照射强度控制药物释放,在农业领域有广阔的应用前景。     

果胶@壳聚糖复合凝胶微球的制备及释药性能EI

文中以天然多糖果胶和壳聚糖为原料,采用乳化交联的方法制备了果胶酸锌微球,再通过自组装壳聚糖层并用柠檬酸钠固化,得到了核壳结构的凝胶微球,将药物奥沙拉嗪封装在凝胶微球中,考察了其药物缓释性能。通过红外光谱、扫描电镜、能谱分析和荧光显微镜对微球形貌和核壳结构进行了表征。通过单因素变量法对凝胶微球的制备进行了优化,并对微球的药物负载性能及在模拟结肠环境中的释药行为进行了研究。结果表明,果胶@壳聚糖载药微球的最高载药量和包封率分别为29.4%和37.3%,果胶@壳聚糖复合载药微球在pH=7.4的模拟结肠液中,前12 h内的释放量仅为35.29%,72 h后奥沙拉嗪的释放量达到了89.90%,而纯果胶载药微球前12 h的释放量就已经高达78.65%,体现了壳聚糖包封层在药物缓释中的重要性。锌离子在果胶@壳聚糖复合微球和果胶微球中的释放趋势与奥沙拉嗪一致,相比于果胶微球,果胶@壳聚糖复合微球具备良好的缓释性能,可用于治疗结肠炎症疾病。     

壳聚糖水凝胶的制备及性能研究

以壳聚糖为原料,用戊二醛作为交联剂,在醋酸溶液中合成壳聚糖水凝胶。用正交实验优化了制备壳聚糖水凝胶的工艺条件,实验结果表明:当壳聚糖浓度为3%、戊二醛浓度为3%、凝胶温度为55℃时制得的水凝胶硬度最大;当壳聚糖浓度为2%、戊二醛浓度为1%、凝胶温度为45℃时,制得的水凝胶溶胀度最大。壳聚糖水凝胶具有良好的生物相容性。     

磁性壳聚糖-聚丙烯酸载药微球的释放性能研究

对合成的壳聚糖-聚丙烯酸及磁性壳聚糖-聚丙烯酸微球用扫描电镜进行形貌观察,并测定了磁性壳聚糖-聚丙烯酸微球的热稳定性。以牛血清白蛋白(BSA)为模拟蛋白药物,研究了载有BSA的磁性壳聚糖-聚丙烯酸微球的释放性能。结果表明,壳聚糖-聚丙烯酸共聚物外形呈片层状;而磁性壳聚糖-聚丙烯酸微球为致密微球,粒径约在100～400 nm之间,具有较好的分散性,磁性壳聚糖-聚丙烯酸微球在温度区间(0～135℃)内具有良好的热稳定性。载有BSA的磁性微球在模拟肠液中刚开始时有一个突释过程,之后缓慢释放,在6h左右达到了平衡,最终释放率可达到80．5%;而在模拟胃液中几乎没有释放,平衡释放率只有5．8%。     

磁性壳聚糖-聚丙烯酸载药微球的释放性能研究

对合成的壳聚糖-聚丙烯酸及磁性壳聚糖-聚丙烯酸微球用扫描电镜进行形貌观察,并测定了磁性壳聚糖-聚丙烯酸微球的热稳定性.以牛血清白蛋白(BSA)为模拟蛋白药物,研究了载有BSA的磁性壳聚糖-聚丙烯酸微球的释放性能.结果表明,壳聚糖-聚丙烯酸共聚物外形呈片层状;而磁性壳聚糖-聚丙烯酸微球为致密微球,粒径约在100～400nm之间,具有较好的分散性,磁性壳聚糖-聚丙烯酸微球在温度区间(0～135℃)内具有良好的热稳定性.载有BSA的磁性微球在模拟肠液中刚开始时有一个突释过程,之后缓慢释放,在6h左右达到了平衡,最终释放率可达到80.5%;而在模拟胃液中几乎没有释放,平衡释放率只有5.8%.     

注射型壳聚糖温敏相变复合材料的制备及性能研究

制备了一种注射型壳聚糖(CS)温敏相变复合材料,首先采用乳化-化学交联法,以戊二醛为交联剂,制备包载甲氨蝶呤(MTX)的壳聚糖微球,然后采用离子交联法,向CS溶液中滴加50%甘油磷酸钠溶液,制备CS温敏水凝胶。将CS载药微球分散于水凝胶中,制得温敏相变复合材料。结果表明,所制得的微球载药量为12.98%,包封率为32.66%,且粒径均一,分散性良好,具有良好的通针性;水凝胶在37℃下1min内可发生相变,由溶胶转变为凝胶,具有良好的温度敏感性;制备的温敏相变复合材料具有良好的原位注射性,且4h内药物释放率为35.65%,缓释效果明显。     

果胶@壳聚糖复合凝胶微球的制备及释药性能EI北大核心CSCD

文中以天然多糖果胶和壳聚糖为原料,采用乳化交联的方法制备了果胶酸锌微球,再通过自组装壳聚糖层并用柠檬酸钠固化,得到了核壳结构的凝胶微球,将药物奥沙拉嗪封装在凝胶微球中,考察了其药物缓释性能。通过红外光谱、扫描电镜、能谱分析和荧光显微镜对微球形貌和核壳结构进行了表征。通过单因素变量法对凝胶微球的制备进行了优化,并对微球的药物负载性能及在模拟结肠环境中的释药行为进行了研究。结果表明,果胶@壳聚糖载药微球的最高载药量和包封率分别为29.4%和37.3%,果胶@壳聚糖复合载药微球在pH=7.4的模拟结肠液中,前12 h内的释放量仅为35.29%,72 h后奥沙拉嗪的释放量达到了89.90%,而纯果胶载药微球前12 h的释放量就已经高达78.65%,体现了壳聚糖包封层在药物缓释中的重要性。锌离子在果胶@壳聚糖复合微球和果胶微球中的释放趋势与奥沙拉嗪一致,相比于果胶微球,果胶@壳聚糖复合微球具备良好的缓释性能,可用于治疗结肠炎症疾病。     

己酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶的制备及其药物缓释性能

为减少泊洛沙姆水凝胶的溶胶-凝胶转变温度对浓度的依赖性,以泊洛沙姆(P₄₀₇)为基材,将己酰化乙二醇壳聚糖(HGC)与泊洛沙姆复合,制备了己酰化乙二醇壳聚糖/泊洛沙姆(HGC/P₄₀₇)复合水凝胶,利用FTIR、SEM及试管反转法探讨了HGC/P₄₀₇复合水凝胶的性能,并利用紫外-可见分光光度计(UV-vis)对HGC/P₄₀₇复合水凝胶的体外药物缓释性能进行表征。结果表明,通过控制HGC的加入量,基于3%泊洛沙姆的HGC/P₄₀₇复合水凝胶即可发生溶胶-凝胶转变现象,并使HGC/P₄₀₇复合水凝胶的溶胶-凝胶转变温度处于32~37℃。HGC/P₄₀₇复合水凝胶具有高度孔隙率,孔隙之间相互连通,孔径大小处于10~90μm的范围之内。HGC/P₄₀₇复合水凝胶对抗癌药物吉西他滨的释药量达到82.4%~90.6%,缓释时间可达80 h左右。HGC/P₄₀₇复合水凝胶在可注射药物载体领域具有重要的应用前景。     

自修复氧化海藻酸钠-羧甲基壳聚糖水凝胶的制备及药物缓释性能

本研究基于动态亚胺键合成了一种具有自修复性能的氧化海藻酸钠-羧甲基壳聚糖水凝胶(OSA-CMCS).通过海藻酸钠的糖醛酸,合成了OSA,并通过与CMCS的席夫碱反应制备了具有不同交联度的自修复OSA-CMCS水凝胶,研究了OSA-CMCS水凝胶的微观形态、黏弹性能、溶胀性能、自修复性能、酶促降解性能和体外药物释放性能....     

Preparation and characterization of chitosan microspheres containing doxifluridine

Chitosan microspheres containing 5-fluorouracil (5-FU), tegafur (FT), and doxifluridine (DFUR) were prepared by the dry-in-oil method using silicone oil with no surfactant as a dispersion medium. For DFUR-containing chitosan microspheres (DFUR-M), reacetylation with acetic anhydride or coating using chitosan and glutaraldehyde was performed. DFUR-M, reacetylated DFUR-M, and chitosan-coated DFUR-M were investigated on in vitro drug release, and the former two microspheres were examined for in vivo degradation after subcutaneous (s.c.) implantation in mice, and in vivo plasma concentration-time profiles after s.c. implantation in rats. The present method gave fairly large microspheres purely composed of chitosan and drug because of no use of surfactant, which showed the mean particle diameters of 300-900 µm and the drug contents of 4-22% (w/w). Encapsulation efficiency of DFUR was higher than that of 5-FU and FT. DFUR-M and reacetylated DFUR-M exhibited spherical shape except chitosan-coated DFUR-M. DFUR-M showed high initial rapid release, which was suppressed to some extent by reacetylation or chitosan coating. DFUR-M and reacetylated DFUR-M subcutaneously implanted were gradually degraded, and approximately half or a little more of the microspheres disappeared from the implanted site at 3 weeks postimplantation. DFUR-M and reacetylated DFUR-M implanted subcutaneously gave similar plasma concentration-time profiles of DFUR, which did not indicate prolonged release in vivo. DFUR-containing chitosan microspheres with fairly large size and good drug content could be obtained by the present preparation but remained to be improved for drug release properties.     

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 pm. The drug loading efficiency of berberine hydrochloride （BH） loaded in microspheres were affected by chitosan （CS） concentration, EC concentration and the volume ratio of V（CS）/V（EC）. ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid （dHCl） and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCI and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.     

壳聚糖-固态分散体载药微球的制备及性能研究

首先采用不同分子量的壳聚糖通过乳化-化学交联法制备了4种不同的壳聚糖载药微球。通过对微球的粒径、溶胀率、载药率、包封率等指标检测以及缓释性能的研究,发现分子量为240kDa的壳聚糖制备的载药微球缓释效果明显,载药率、包封率均较高,综合性能优于其它分子量壳聚糖制备的微球。利用该分子量壳聚糖包埋固态分散体制备了壳聚糖-固态分散体载药微球,改善了药物的溶解性并具有药物缓释作用。因此,壳聚糖-固态分散体载药微球是一种理想的药物缓释体系,可以用于包埋溶解性差,生物半衰期短,对胃肠刺激性强的药物。     

Preparation and properties of calcium sulfate bone cement incorporated with silk fibroin and Sema3A-loaded chitosan microspheres

To search for new bioactive materials which can be used as the substitute of bone repairing and drug carriers, Sema3A-loaded chitosan microspheres (SLCM) and silk fibroin (SF) were mixed with calcium sulfate cement (CSC). SEM, particle size analysis and swelling rate determination were performed to study properties of the microspheres. The drug loading, encapsulation efficiency and drug release rate were determined by ELISA. Microspheres with different SLCM weight contents (0.5%, 1% and 5%) were prepared to determine which one has the strongest mechanical properties and the appropriate setting time. It was revealed that CSC/SF/0.5SLCM has satisfactory mechanical properties, and its in vitro biocompatibility was assessed by MTS. Chitosan microspheres (5--18 μm) were globular, the surface was smooth, and the swelling rate is (77.02±5.57)%. With this formula, the setting time was increased with the addition of SLCM in CSC/SF, and the cumulative drug release rate is 44.62% in 28 d. XRD results demonstrate that the main component is calcium sulfate. Also it was found that CSC/SF/0.5SLCM supports the growth of MC3T3 cells. Thus the preparation of CSC/SF/0.5SLCM was reliable, and the products had good structures, physical properties and biocompati-bility, appearing to be a promising bone substitute material.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

CS/PMA30水凝胶的制备及其对中性红控释性能的研究

将聚阳离子壳聚糖(CS)与聚阴离子甲基丙烯酰氧乙基磷酰胆碱-甲基丙烯酸二元共聚物(poly(MPC-co-MA),PMA30)进行静电复合,制备CS/PMA30聚离子水凝胶,并用红外(IR)、扫描电镜(SEM)分别对其特征官能团、表面形貌进行表征。然后,以中性红为模型药物对CS/PMA30水凝胶的控释性能进行研究。结果表明,CS/PMA30体系是通过静电作用形成的物理交联水凝胶,对模型药物中性红具有明显的控释性和pH值响应性。该水凝胶具有良好生物相容性有望在药物控释、组织工程等领域具有巨大的应用前景。该研究为进一步提高水凝胶的生物相容性提供了一个新的途径。