SPG膜乳化法制备单分散性载药微囊

发布时间：2018-04-09 17:43

本文选题：生物降解高分子　切入点：药物控释　出处：《长春工业大学》2010年硕士论文

【摘要】：在药物控释体系中,大多数的多肽、蛋白质类药物都是水溶性的,而作为包埋材料的生物可降解高分子则是油溶性的,这给载药微囊的制备造成了很大的困难。水包油包水(W/O/W)复乳溶剂蒸发法的出现有效的解决了该问题,在药物控释领域得到了广泛的应用。在制备过程中,通常采用超声、均质或机械搅拌等手段制备水包油包水(W/O/W)型双乳液。但无论采用上述何种制备方法,制备过程中都容易出现包封率低、微球中药物释放的突释及药物在微囊内聚集或失活等问题,限制了该方法在实际中的应用。上世纪90年代开发的膜乳化技术有效的解决了上述问题。膜乳化技术是一种新型的乳液制备手段,具有能耗低、操作简单、重复性好、得到的产品粒径分布窄并可有效的对产品尺寸进行控制等明显优点。首先,论文为了考察实验条件对制备载药微囊的影响,研究了乳化剂种类、乳化剂浓度以及有机溶剂的密度等因素对初乳稳定性的影响,以及膜乳化压力、搅拌速度和固化时间对载药微囊包封率的影响,并对其体外释放行为进行了考察。本章实验均以乙交酯和丙交酯的无规共聚物(PLGA)为载体材料,BSA为模型蛋白。分析表明,随着膜乳化压力的增加,包封率会不同程度的降低；搅拌速度的增加也会导致包封率的降低；固化时间为5h时,包封率最高。而后,论文还研究了初乳液滴尺寸对膜乳化法制备载药微囊性质的影响。通过实验,我们发现初乳液滴尺寸对载药胶囊的表面形态、包封率及释放行为均有重要的影响。结果表明,随着初乳液滴尺寸的减小,载药微球表面孔洞的直径也随之减少,表面变光滑,包封率逐渐提高,最大包封率达到90%以上；初乳液滴尺寸越小,载药微囊的突释现象越不明显,体外释放行为越平稳。其次,论文采用PLGA为载体材料,BSA为模型蛋白,采用膜乳化技术结合水包油包水(W/O/W)复乳溶剂蒸发法制备BSA载药微囊。结果表明：膜乳化法制备的载药微囊的包封率明显高于机械搅拌法,最高可达93.72%；采用膜乳化技术,可以有效的缓解载药微囊的突释现象,1个月内的累计释放量可以达到80%以上。最后,论文对膜乳化法结合水包油包固体(S/O/W)法制备载胰岛素微囊进行了探索。首先,实验采用等电点沉淀法成功制备出了胰岛素纳米颗粒,其粒径分布范围主要在30-50nm之间；其次,采用S/O/W法结合膜乳化技术制备胰岛素载药微囊,并对得到的载药微囊进行表征,结果表明：采用S/O/W法制备的载药微囊表面的孔洞相对较少,表面比较光滑；该方法制备的载药微囊包封率较低,最高仅能达到71.55%；与此同时,载药微囊的突释量较低,从整个释放行为上看,该方法制备的载药微囊的释放行为可持续两周左右。
[Abstract]:In drug controlled release system, most polypeptides and protein drugs are water-soluble, while biodegradable polymers as encapsulated materials are oil-soluble, which makes the preparation of drug-loaded microcapsules very difficult.The water / oil / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / waterIn the process of preparation, ultrasonic, homogenization or mechanical stirring are usually used to prepare water / oil / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / waterHowever, no matter what kind of preparation method mentioned above, it is easy to have low entrapment efficiency in the preparation process. The sudden release of the drug in the microspheres and the aggregation or inactivation of the drugs in the microcapsules limit the application of the method in practice.The membrane emulsification technology developed in the 90's of last century effectively solved the above problems.Membrane emulsification is a new method of emulsion preparation, which has the advantages of low energy consumption, simple operation, good repeatability, narrow particle size distribution and effective control of product size.The effects of stirring speed and curing time on encapsulation efficiency of drug loaded microcapsules were investigated.In this chapter, BSA was used as the model protein, and the random copolymers of glycolide and lactide were used as the carrier material.The results show that the entrapment efficiency decreases with the increase of emulsification pressure, the entrapment efficiency decreases with the increase of stirring speed, and the encapsulation efficiency is the highest when the curing time is 5 h.Then, the effect of the size of colostrum droplets on the properties of drug-loaded microcapsules prepared by membrane emulsification was also studied.Through experiments, we found that the size of colostrum droplets has an important effect on the surface morphology, encapsulation efficiency and release behavior of drug-loaded capsules.The results show that with the decrease of the size of colostrum droplets, the diameter of pores on the surface of the drug-loaded microspheres decreases, the surface becomes smooth, the encapsulation efficiency increases gradually, the maximum encapsulation efficiency reaches more than 90%, and the smaller the size of the droplets, the smaller the size of the droplets.The less obvious the sudden release of drug-loaded microcapsules, the more stable in vitro release behavior.Secondly, the drug carrying microcapsules of PLGA were prepared by using membrane emulsification and water in oil / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water / water (W / O / W) composite emulsion as solvent evaporation method.The results showed that the encapsulation efficiency of the drug-loaded microcapsules prepared by membrane emulsification method was obviously higher than that by mechanical stirring method and the highest was 93.722.Using membrane emulsification technology, the phenomenon of sudden release of drug-loaded microcapsules could be effectively alleviated, and the cumulative release amount could reach more than 80% within one month.Finally, the preparation of insulin-loaded microcapsules by membrane emulsification combined with water-in-oil solid S / O / W method was investigated.Firstly, insulin nanoparticles were successfully prepared by isoelectric precipitation method, whose particle size distribution was mainly between 30-50nm. Secondly, insulin loaded microcapsules were prepared by S/O/W method combined with membrane emulsification technology.The results show that the microcapsules prepared by S/O/W method have relatively few pores and smooth surface, and the encapsulation efficiency of the microcapsules prepared by this method is lower, the highest encapsulation efficiency is only 71.55%, and at the same time, the encapsulation efficiency of the microcapsules prepared by this method is 71.55 and 71.55 respectively, and the encapsulation efficiency of the microcapsules prepared by this method is only 71.55.The sudden release of drug loaded microcapsules was relatively low, and the release behavior of the microcapsules prepared by this method lasted for about two weeks in terms of the whole release behavior.
【学位授予单位】：长春工业大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R318.08

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