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海藻酸钠微胶囊的新型制备方法及应用
Alternative TitleNovel Preparation Methods and Applications of Alginate-based Microcapsules
张岳玲
Subtype博士
Thesis Advisor王连艳
2011-11-24
Degree Grantor中国科学院研究生院
Place of Conferral北京
Degree Discipline生物化工
Keyword海藻酸钠微胶囊 微孔膜乳化 粒径控制 包埋与控释 表征及应用
Abstract微胶囊技术是一项具有很高实用价值并已经被广泛应用的先进技术,微胶囊化可以保护芯材并使其获得更多特殊功能。海藻酸钠由于具有良好的生物相容性、生物粘附性和温和的凝胶条件已被广泛应用于医药、农药、食品、化妆品等许多领域。虽然海藻酸钠微胶囊的制备方法有多种,但绝大多数方法无法工业化而且制备的微胶囊粒径偏大;而传统乳化技术虽能得到粒径相对较小微胶囊,但无法保证其均一性。本论文的研究目在于发展粒径均一、可控并对于水溶性物质、脂溶性物质和益生菌类物质的包埋具有普适性的海藻酸钠微胶囊,主要以易于工业化的微孔膜乳化法结合离子固化法制备了粒径均一的海藻酸钠/壳聚糖复合微胶囊,同时针对膜乳化-固化法所得海藻酸钠微胶囊在包埋脂溶性物质和益生菌方面的不足,以LBL(Layer-by-layer)层层自组装法和喷雾-离子固化法制备了其它类型的海藻酸钠微胶囊。本论文共分为四部分,第一部分将微孔膜乳化法(W/O体系)和离子固化法相结合制备海藻酸钠微胶囊。通过对固化剂的加入方式和固化步骤的探索,解决了海藻酸钠液滴与Ca2+被油相阻隔无法直接接触固化的问题,制备出了粒径均一的具有良好球形和分散性的海藻酸钠/壳聚糖微胶囊。对微胶囊的制备条件进行优化并从微胶囊的机械强度方面分析了由组分含量不同引起的微胶囊性质差异。第二部分对微胶囊的内部结构、表面形态、表面电荷以及pH敏感性进行表征后,以胰岛素作为水溶性蛋白质、多肽等药物的模型进行微囊化,由于胰岛素被均匀包埋在微囊内,微囊显示了稳定的释放行为;采用糖尿病模型大鼠评估载胰岛素微胶囊的药效,可以观察到长期而良好的降血糖效果,说明制备的粒径均一的载胰岛素海藻酸钠/壳聚糖复合微胶囊是一种潜在的胰岛素的口服给药载体,并且也为其它的蛋白质、多肽类药物的口服给药提供了借鉴。第三部分将膜乳化法与O/W/O复乳法相结合,以葵花籽油作为脂溶性物质的模型,制备出粒径均一的包埋不同尺寸油滴的海藻酸钠/壳聚糖微胶囊。由于膜乳化法制备的含有葵花籽油的微胶囊粒径至少为10 μm,本部分又以LBL电荷沉积技术将粒径均一的、约为10 μm的葵花籽油液滴表面包裹多层海藻酸钠和壳聚糖,形成包含油滴的微胶囊。而且由于粒径越小的液滴,越容易采用此方法形成微胶囊,所以该方法可作为对膜乳化法制备包含油滴的海藻酸钠微胶囊的补充,拓宽微胶囊的粒径范围。两种方法制备的微胶囊均可推广于其它脂溶性物质的包埋和保护。第四部分以表达了苯丙氨酸脱氨酶的乳酸菌(LLEP)为益生菌模型,首先采用微孔膜乳化法结合离子固化法将其微囊化,结果发现该方法无法制备具有高包埋量和活性保持率的包埋LLEP的海藻酸钙微胶囊,而由喷雾固化法制备的海藻酸钙微胶囊则具有高包埋量(LLEP的浓度最高为17.0 wt%)和活性保持率(92.2%);体内药效评估显示该微胶囊具有减缓因食用正常食物引起的体内苯丙氨酸浓度升高的效果,而且在停止给药后短期内(3 天)还可以稳定苯丙氨酸浓度。综上,本论文采用微孔膜乳化法结合离子固化法制备的粒径均一的海藻酸钠微胶囊可以成功实现对水溶性物质模型——胰岛素的包埋并有效改善胰岛素的口服给药疗效;脂溶性物质模型——葵花籽油的微囊化可以根据所需粒径范围选择由膜乳化结合离子固化或层层自组装法制备,所得微胶囊粒径分布较窄并表现出良好的应用效果;而喷雾固化法制备的海藻酸钠微胶囊也解决了益生菌类模型——LLEP在应用时存在的问题。因此,本论文发展的海藻酸钠微胶囊的制备方法不仅解决了现有方法中存在的问题,提高了应用效果,而且可适用于不同类型芯材,拓宽了该微胶囊的应用前景。
Other AbstractMicroencapsulation technology can protect core materials and endow them with multi-functions. As a wall material of microencapsulation, alginate is widely used in the fields of medicine, pesticide, food, cosmetic due to its excellent biocompatibility, mucoadhesiveness and mild gelation. However, the size of obtained alginate microcapsules was too large and microcapsules were difficult to be manufactured in large scale by most of current preparation methods. Although smaller alginate microcapsules can be prepared by traditional emulsification technology, unfortunately, the size distribution was broad. Therefore, the objective of this thesis was to develope novel preparation methods, which not only provide alginate microcapsules with uniform and controllable size, but also were suitable for encapsulating various types of core materials, such as hydrophilic materials, hydrophobic materials and probiotics. This thesis mainly included the following four parts. In the first part, the alginate microcapsules with uniform-size, good sphericity and dispersity were prepared from W/O system by membrane emulsification combined with ion-solidification process. It was found that the utilization of CaCl2 mini-emulsion and two-step solidification in the process was decisive for the successful preparation. Afterwards, the preparation conditions of alginate microcapsules were optimized to achieve a higher yield. Further characterizations of the amount of Ca and chitosan in the microcapsules revealed that the different mechanical strength of microcapsules was induced by their different composition. In the second part, the morphology, surface charge properties, interior structure and pH sensitivity of alginate microcapsules were examined. Then, insulin was loaded in the microcapsules as the model of hydrophilic peptide drug. The microcapsules showed a constant release behavior due to the homogeneous encapsulation state of insulin. Furthermore, the blood glucose level of diabetic rats could be effectively reduced and stably kept for a long time (~60 h) after oral administration of the insulin-loaded alginate/chitosan microcapsules. In the third part, sunflower oil was used as the model of hydrophobic materials and encapsulated in the alginate microcapsules from O/W/O system by membrane emulsification technique. However, only the microcapsules larger than 10 μm could be prepared due to the nagative effect of primary emulsion. Hence, to prepare smaller alginate microcapsules containing oil, LBL (layer-by-layer) technique was employed to layer alginate and chitosan on the uniform-sized sunflower oil droplets, which were produced by porous membrane emulsification. The oxidation stability of sunflower oil in the multi-layered microcapsules was improved, which indicated that this microcapsule was useful to protect other hydrophobic core material. In the fourth part, as the model of probiotics, Lactococcus lactis-expressing phenylalanine ammonia-lyase (LLEP) was encapsulated in the alginate microcapsules by the same method as in the first part. Nevertheless, this method could not realize higher encapsulate efficiency and good protection to the bioactivity of LLEP. Therefore, spray-ion-solidification was developed to achieve microcapsules with higher encapsulation efficiency and bioactivity retention of LLEP. The animal test results showed that the increase of the blood phenylalanine (Phe) level was significantly slowed down after a 7 day treatment with oral administration of LLEP-encapsulated microcapsules. In conclusion, new preparation methods of alginate-based microcapsules were established in this study, which not only overcame the disadvantages of current techniques, but also could be applied to the encapsulation of different core materials.
Document Type学位论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/1755
Collection研究所(批量导入)
Recommended Citation
GB/T 7714
张岳玲. 海藻酸钠微胶囊的新型制备方法及应用[D]. 北京. 中国科学院研究生院,2011.
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