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。     

微球型壳聚糖胺基吸附剂的制备及性能

以壳聚糖为原料,采用反相悬浮交联的方法制取微球型壳聚糖颗粒,再进行羟丙基氯化及胺基化,制备了一系列新型壳聚糖胺基衍生物微球。衍生物的胺基含量明显提高,碱性增强。并初步考察其吸附牛血清白蛋白（ＢＳＡ）性能。可用作新固定化酶载体及生化分离材料。     

丝素-羟丙基壳聚糖微球的结构和释药性能

以胰岛素为目标药物,以丝素(SF)和羟丙基壳聚糖(HPCS)为包药材料,复凝聚法制备SF-HPCS载药微球。采用红外光谱(FTIR)、扫描电镜(SEM)、X射线衍射(XRD)、热重分析(TGA)等对载药微球的结构、外部形貌及热性能等进行了表征。结果表明,所制备的载药微球表面密实,平均粒径22.4μm,呈正态分布;载药微球对胰岛素的包埋率达73.6%,大于HPCS载药微球(64.3%)及壳聚糖(CS)载药微球(57.1%);SF-HPCS载药微球在人工胃液中4h内累计释药率为21.3%,在人工肠液中24h内累计释药率达81.2%,48h累计释药率为92.2%,释放过程平稳、缓慢。     

交联壳聚糖树脂的制备及其对Cu~(2+)吸附性的研究

以壳聚糖为原料,制成壳聚糖微球,再经过环氧氯丙烷交联得到羟丙基氯壳聚糖微球。实验研究了2.8%壳聚糖醋酸溶液,致孔剂20%无水乙醇,15%氢氧化钠,壳聚糖与环氧氯丙烷质量比为2∶1,反应θ为50℃,反应t为4 h,得到最好的羟丙基氯壳聚糖微球。当溶液pH=6时,振荡θ为30℃,振荡t为60 min,对Cu2+有最大吸附量。     

超临界抗溶剂法制备吲哚美辛-羟丙基-β-环糊精微球

采用超临界抗溶剂法制备吲哚美辛-羟丙基-β-环糊精复合微球。在单因素试验的基础上设计正交试验优选吲哚美辛-羟丙基-β-环糊精微球的制备工艺,并考察其体外溶出度。在最优工艺条件下吲哚美辛-羟丙基-β-环糊精复合微球的平均载药量为66. 04%。扫描电镜所得结果表明所制得的吲哚美辛复合微球为不规则絮状。傅里叶红外吸收光谱和差示扫描量热表明所制得的吲哚美辛与羟丙基-β-环糊精形成了复合结构。溶出实验表明产吲哚美辛复合微球达到平衡的时间相较于其原料有很大延缓,从而在保证药物溶出的前提下具备缓释效应。     

壳聚糖吸附剂的制备及性能

通过以壳聚糖为原料,经交联、羟丙基氯化及胺基化,制备了壳聚糖胺基吸附剂。经红外光谱和扫描电镜测定其结构,研究了不同的胺化试剂及其用量对壳聚糖吸附剂胺基含量的影响及对中药液中黄酮化合物的吸附性能。结果表明,改性壳聚糖微球胺基含量比壳聚糖高,对游离黄酮的吸附量随着胺基含量增加而增加。     

阿维菌素凝胶微球制备及其缓释性能研究

以壳聚糖(CS)和海藻酸钠(ALG)为包封材料,以阿维菌素(AVM)为芯材,采用锐孔法制备了阿维菌素-海藻酸钠-壳聚糖微球,考察了海藻酸钠质量分数、壳聚糖质量分数、氯化钙质量分数和芯壁体积比(质量分数1%的阿维菌素乳液与质量分数3%海藻酸钠溶液的体积比)对微球形态及包埋率的影响,利用SEM、FTIR等对微球结构及性质进行了表征,并考察了其在土壤中的缓释性能和释药机制。结果表明,经优化的制备条件为:海藻酸钠、壳聚糖及氯化钙的质量分数分别为3%、0.6%及5%,芯壁体积比为1∶2,制备的载药微球形状规整,成球性良好,粒径约0.7 mm,载药量31.65%,包埋率83.81%;红外光谱分析显示,芯壁材料之间除氢键外,没有发生化学作用。所制备的阿维菌素微球在土壤中具有缓释特性,42 h累积释药率达到82.06%,之后药物释放减缓。药物释放特性符合Riger-Peppas模型,释放机理为Fick扩散。     

壳聚糖/明胶复合微球的制备及吸附性能研究

以壳聚糖和明胶为原料,span 80为乳化剂,戊二醛为交联剂,采用乳化交联法制备了壳聚糖/明胶复合微球并用于Cr(Ⅵ)的吸附。考察了复合微球的各制备因素对微球形貌的影响,通过单因素分析研究了壳聚糖与明胶的比例、乳化剂用量、乳化时间对复合微球吸附性能的影响。结果表明,壳聚糖与明胶的比例为1∶2、span80用量为6mL、乳化时间为50min时,制备的复合微球对Cr(Ⅵ)的吸附性能良好,吸附量较大,Cr(Ⅵ)的去除率可达95.3%。     

磁性壳聚糖微球的制备及其固定化乳糖酶的研究

采用水热法制备得到磁性Fe_3O_4纳米粒子,以壳聚糖、制备的Fe_3O_4为原料,采用乳化交联法成功制备了磁性壳聚糖微球,并通过SEM、FTIR、VSM、XRD对其进行表征。进一步以制备的磁性壳聚糖微球为载体,采用吸附法制备磁性壳聚糖微球固定化乳糖酶。以酶活力为考察指标,研究了不同固定化条件对制备固定化酶的影响,以及固定化酶的酶学性质。结果表明,乳糖酶的最佳固定化条件为:固定化时间4 h,pH为7.0,乳糖酶酶液浓度为0.6 mg/mL,固定化酶相对于游离酶的pH稳定性和温度稳定性均有一定程度的提高,固定化酶重复使用5次后,酶活仍保留65%以上。     

磁性硅基壳聚糖微球固定化柚苷酶水解柚皮苷的研究

本文在磁性Fe3O4外包覆一层SiO2,再在其外包裹壳聚糖制备出磁性硅基壳聚糖微球（MSC）,对MSC进行环氧基修饰后用于柚苷酶的固定化研究,并对磁性硅基壳聚糖微球固定化柚苷酶水解柚皮苷的pH、温度、操作和储藏稳定性进行了考察。通过单因素实验,确定了环氧基修饰的磁性硅基壳聚糖微球（MSCE）固定化柚苷酶的最佳工艺条件为：pH 3.0,温度30 ℃,时间4 h、给酶量57.48 U/mL。在此条件下,MSCE固定化柚苷酶的载酶率、酶活回收率和酶比活力分别为31.29%、88.92%和409.33 U/g。与游离柚苷酶相比,MSCE固定化柚苷酶用于水解柚皮苷具有良好的pH稳定性和温度稳定性,重复使用8次后仍具有53.36%的相对酶活力,4 ℃条件储存一个月后仍具有80.97%的相对酶活力。     

Synthesis,characterization, and microsphere formation of galactosylated chitosan

Chitosan derivative with galactose groups, which was recognized specifically by the asialoglycoprotein receptor (ASGR), was synthesized by introduction of the galactose group into the amino group of chitosan. The chemical structure of galactosylated chitosan was characterized by FT‐IR, ¹H‐NMR, ¹³C‐NMR, WAXD, and DSC techniques. The results indicated that although acyl reaction on the part of amino groups of chitosan took place, the degree of galactosylated substitution was 20%, and the crystallization, solubility, stability, and other physical properties were different from chitosan. Microspheres of chitosan and galactosylated chitosan were prepared by the physical precipitation and coacervation method with sodium sulfate, respectively. The characterizations of microspheres were determined by means of scanning electron microscopy (SEM), particle size/ζ potential analysis, and DSC methods. Spherical, positively charged chitosan and galactosylated chitosan microspheres were formed, with an average diameter of 0.54 and 1.05 μm, and average ζ potential of +17 mV and +15 mV, respectively. The novel galactosylated chitosan microspheres may be used as a potential drug delivery system with passive and active hepatic targeting properties. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 659–665, 2004     

载胰岛素壳聚糖微球口服降血糖作用的研究

为了研制一种生物利用度高且具有缓释作用的口服胰岛素制剂,采用静电液滴工艺制备载胰岛素壳聚糖-海藻酸钙微球,以四氧嘧啶为诱导剂建立糖尿病小鼠模型,采用葡萄糖氧化酶法测定小鼠血糖含量,对载药微球的口服药效学进行评价。结果表明:载胰岛素微球平均粒径48μm,药物包封率94.1%,胰岛素相对活性71.7%;药效学研究表明,口服高(4.8 IU/kg)、中(3.6 IU/kg)、低(2.4 IU/kg)3种剂量胰岛素微球,糖尿病小鼠相对血糖值口服6 h时降至最低,分别为42.69%,59.8%,76.13%,药理相对生物利用度为41.20%,37.76%,35.81%。口服载胰岛素壳聚糖-海藻酸钠微球具有降血糖作用和显著的缓释作用,药理相对生物利用度高。     

星点设计-效应面优化乳化交联法制备恩诺沙星壳聚糖微球

以平均粒径、载药量、包封率及总评归一值为评价指标,运用星点设计考察芯材比、油水相比、壳聚糖浓度对微球制备的影响,对结果进行二项式拟合,效应面法选取最佳工艺条件并进行预测分析。结果显示,最佳工艺条件为：油水相比为4.2∶1,壳聚糖浓度为2%,交联时间为3.5 h。在此条件下,制得的微球粒径均一,球形圆整,平均粒径为7.21μm,包封率为61.34%,载药量为70.12%。体外释放行为符合Higuchi方程,2 h和24 h时累积释放率分别为32%和84%。     

Synthesis and characterization of injectable chitosan cryogel microsphere scaffolds

Treatment of tissue defects involves invasive processes such as implanting the tissue engineered scaffold to the defected area. Injectable scaffolds are increasingly being developed to achieve tissue regeneration in a less invasive manner. In this study, injectable chitosan cryogels in the form of microspheres were synthesized combining the water in oil emulsification method with the crosslinking of microspheres during cryogelation. The effects of polymer ratio, crosslinker concentration, cryogelation temperature, and stirring speed on the resulting cryogels’ chemistry, pore morphology, microsphere size, swelling ratio, degree of crosslinking, and degradation rate were examined for a possible noninvasive tissue engineering application. Microspheres with optimized properties were developed with an average pore and particle size of 5.50?±?0.63 and 220.11?±?25.58?µm at a chitosan ratio of 1%, glutaraldehyde concentration of 3%, reaction temperature of ?16°C, and stirring rate of 1,000?rpm.     

A novel insulin oral delivery system assisted by cationic β‐cyclodextrin polymers

This work describes a new oral pharmaceutical formulation of insulin that is complexed with cationic β‐cyclodextrin polymers (CPβCDs), and then encapsulated into alginate/chitosan microspheres, which are prepared by ionotropic pregelation/polyelectrolyte method. CPβCDs were synthesized through a one‐step polymerization of β‐cyclodextrin (βCD), epichlorohydrin, and choline chloride. CPβCDs have enhanced ability to complex with insulin due to the assistance of their polymeric chains, as well as the electrostatic interactions between insulin (negatively charged while pH>5.3) and quaternary ammonium groups of CPβCDs. The noncovalent inclusion complex formed between CPβCDs and insulin was analyzed by Fourier transform infrared and fluorescence emission spectra. With the increase of zeta potential of CPβCDs from 1.8 to 14.2 mV, the insulin association efficiency (AE) of current system was increased from 55.2 to 71.8%, whereas the AE of insulin‐loaded microspheres at the same condition was only 50.7%. The cumulative insulin release in simulated intestinal fluid was also higher than that of the insulin‐loaded microspheres and βCD‐insulin encapsulated microspheres. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin

Microspheres were prepared from carboxymethylated chitosan (CM‐chitosan) and alginate by emulsion phase separation. Their structure and morphology were characterized with IR spectroscopy and scanning electron microscopy. Bovine serum albumin (BSA) was encapsulated in the microspheres to test the release behavior. The swelling behavior, encapsulation efficiency, and release behavior of BSA from the microspheres at different pHs and with a pH‐gradient condition were investigated. The BSA encapsulation efficiency was calculated to be 80%. The degree of swelling of the microspheres without BSA loaded at pH 7.2 was much higher than that at pH 1.0. The encapsulated BSA was quickly released in a Tris–HCl buffer (pH 7.2), whereas a small amount of BSA was released under acid conditions (pH 1.0) because of the strong electrostatic interaction between ? NH₂ groups of CM‐chitosan and ? COOH groups of alginic acid and a dense structure caused by a Ca²⁺ crosslinked bridge. For the simulation of the processing of the drug under the conditions of the intestine, the microspheres were tested in a pH‐gradient medium, in which an acceleration of the release occurred at pH 7.4 after a lag time at a low pH (5.8–6.8). At pH 7.4, a large amount of BSA was released from the microspheres in a short time because of the rapid swelling of the microspheres. However, the release only depended on the diffusion of BSA at relatively low pHs, this resulted in a relatively low release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 878–882, 2004     

磁性壳聚糖微球的制备及其用于甲酸脱氢酶的固定化

分别采用乳化交联法和共沉淀法制备磁性壳聚糖微球载体,并对形貌结构进行比较,结果表明,采用共沉淀法制备的磁性壳聚糖微球负载Fe3O4的效果好,故将其作为载体固定甲酸脱氢酶。最佳固定化条件:添加酶量9 U.g-1,pH=7.0,固定化时间5 h。游离酶和固定化酶的最适宜反应温度分别为50℃和30℃;游离酶的最适宜pH=7.0,固定化酶的最适宜pH=6.0;将游离酶和固定化酶分别置于60℃恒温水浴放置180 min后,游离酶和固定化酶的相对酶活力分别为0.78%和40.39%;将游离酶和固定化酶置于不同pH的缓冲液中保存1 h后,在强酸(pH=2.0)和强碱(pH=10.0)条件下,固定化酶的相对酶活力分别为11.03%和38.43%,游离酶已全部失活;固定化酶重复使用6次后,相对酶活力为73.53%,表明固定化酶具有较好的热稳定性、酸碱稳定性和操作稳定性。     

壳聚糖-琼胶复合微球的制备及其药物释放性能

采用小分子离子交联法制备了pH值敏感的壳聚糖-琼胶复合微球,对壳聚糖-琼胶复合微球的粒径、形貌、pH值敏感性等进行了表征.以茶碱为模型药物研究了壳聚糖-琼胶复合微球的药物释放性能,结果发现一定量琼胶的引入有助于改善壳聚糖微球的药物缓释性能.     

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。