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复凝聚和喷雾干燥微囊化后的β-葡萄糖醛酸酶活性

beta-Glucuronidase activity following complex coacervation and spray drying microencapsulation.

作者信息

Burgess D J, Ponsart S

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269, USA.

出版信息

J Microencapsul. 1998 Sep-Oct;15(5):569-79. doi: 10.3109/02652049809008241.

Abstract

The objective was to develop a microencapsulation process suitable for the controlled release of an active protein drug. beta-glucuronidase was selected as a model protein and a combination of complex coacervation (gelatin/sodium alginate, gelatin/acacia and albumin/acacia) and spray drying was investigated. Coacervates were either spray dried or glutaraldehyde crosslinked to form microcapsules. Polyvinylpyrrolidone (PVP) and polyethylene glycol were investigated as potential coacervate enhancers and stabilizers. beta-glucuronidase/polymer mixtures were spray dried to determine any polymer protective effects on protein activity. A BUCHI 190 Spray Drier was used, beta-glucuronidase activity was determined using a Sigma Kit and microcapsule particle size was measured by Accusizer analysis (light blockage). All non-crosslinked coacervates investigated, with the exceptions of albumin/acacia and albumin/acacia/beta-glucuronidase/PVP, were unsuitable for spray drying as they rapidly phase separated and blocked the spray drier nozzle. beta-glucuronidase activity in the albumin/acacia coacervates approximated to 99% prior to and 80% following spray drying. This can be compared to activities of approximately 30% and 68% when spray dried alone and with albumin, respectively, and of 18% in albumin/acacia microcapsules crosslinked with glutaraldehyde. Microcapsule particle size was affected by coacervation pH, additives and spray drying. In vitro beta-glucuronidase release was biphasic, with an initial burst release followed by a zero order release phase and continued over the 12 day study period. In conclusion, the spray drying albumin/acacia/PVP method described is useful for the preparation and collection of controlled release microcapsules with minimal loss of beta-glucuronidase activity.

摘要

目的是开发一种适合活性蛋白药物控释的微囊化工艺。选择β-葡萄糖醛酸酶作为模型蛋白,并研究了复合凝聚(明胶/海藻酸钠、明胶/阿拉伯胶和白蛋白/阿拉伯胶)与喷雾干燥相结合的方法。凝聚层通过喷雾干燥或戊二醛交联形成微胶囊。研究了聚乙烯吡咯烷酮(PVP)和聚乙二醇作为潜在的凝聚增强剂和稳定剂。对β-葡萄糖醛酸酶/聚合物混合物进行喷雾干燥,以确定聚合物对蛋白质活性的保护作用。使用Buchi 190喷雾干燥器,使用Sigma试剂盒测定β-葡萄糖醛酸酶活性,并通过Accusizer分析(光阻法)测量微胶囊粒径。除白蛋白/阿拉伯胶和白蛋白/阿拉伯胶/β-葡萄糖醛酸酶/PVP外,所有研究的非交联凝聚层均不适合喷雾干燥,因为它们会迅速相分离并堵塞喷雾干燥器喷嘴。白蛋白/阿拉伯胶凝聚层中β-葡萄糖醛酸酶的活性在喷雾干燥前约为99%,喷雾干燥后为80%。相比之下,单独喷雾干燥时活性约为30%,与白蛋白一起喷雾干燥时活性约为68%,在与戊二醛交联的白蛋白/阿拉伯胶微胶囊中活性为18%。微胶囊粒径受凝聚pH值、添加剂和喷雾干燥的影响。体外β-葡萄糖醛酸酶释放呈双相性,初始有一个突释阶段,随后是零级释放阶段,并在12天的研究期内持续。总之,所描述的喷雾干燥白蛋白/阿拉伯胶/PVP方法可用于制备和收集β-葡萄糖醛酸酶活性损失最小的控释微胶囊。

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