Controlled release of a model protein from enzymatically degrading dextran microspheres
Controlled release of a model protein from enzymatically degrading dextran microspheres
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DOI：
10.1016/s0168-3659(98)00193-x
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发表时间：
1999-05-20
影响因子：
10.8
通讯作者：
Hennink, WE
中科院分区：
文献类型：
--
作者：
Franssen, O;Stenekes, RJH;Hennink, WE
采用水包水乳液法制备了葡聚糖蛋白质微球。利用这种技术，将甲基丙烯酸化葡聚糖(Dex-MA)的水溶液在聚乙二醇水溶液中乳化。随后，分散的Dex-MA相通过右旋糖苷键合的甲基丙烯酰基的自由基聚合而交联。这种方法制备的微球具有水凝胶特性，其交联度可以通过DEX-MA的水分含量和取代度(DS，每100个吡喃葡萄糖残基中的甲基丙烯酸酯数量)来控制。如果在聚合反应前在Dex-MA/PEG水体系中加入一种免疫球蛋白溶液，则可以将蛋白质以较高的产率(88-98%)包埋在葡聚糖微球中。考察了微球的含水率、取代度和降解率对微球中免疫球蛋白释放的影响。微球通过共包裹内切-葡聚糖酶而变得可降解。非降解微球主要表现为突释，且随交联度的增加而降低。通过低水含量(50%，w/w或更低)或高DS(DS 13)，有可能将猝发释放减少到约10%，这意味着可以实现对蛋白质的几乎完全包埋。降解微球中的免疫球蛋白的释放主要依赖于DS和包埋的葡聚糖酶的量。在高取代度(DS 13)条件下，加入和不加入葡聚糖酶的微球中的免疫球蛋白释放没有差异。这归因于酶不能降解这些微球。另一方面，DS-4酶降解微球中的蛋白质被完全释放。此外，免疫球蛋白的释放速率与微球的降解速率成正比(取决于共包裹的葡聚糖酶的量)。有趣的是，这些微球在长达30天的时间内几乎零级释放。(C)1999由爱思唯尔科学公司出版。版权所有。
Protein-loaded dextran microspheres were prepared by a water-in-water emulsion technique. With this technique, an aqueous solution of methacrylated dextran (dex-MA) is emulsified in an aqueous solution of poly(ethylene glycol) (PEG). Subsequently, the dispersed dex-MA phase is crosslinked by radical polymerization of the dextran-bound methacryloyl groups. This method renders microspheres with a hydrogel character of which the crosslink density can be controlled by the water content and the degree of substitution of the dex-MA (DS, the number of methacrylates per 100 glucopyranose residues). If an IgG solution was added to the dex-MA/PEG aqueous system prior to the polymerization reaction, the protein could be encapsulated in the dextran microspheres with a high yield (88-98%). The release of IgG was studied as a function of the water content, the DS and the degradation rate of the microspheres. The microspheres were rendered degradable by co-encapsulation of an endo-dextranase. Non-degrading microspheres mainly showed a burst release, which decreased with increasing crosslink density. By either a low water content (50%, w/w, or lower) or a high DS (DS 13), it was possible to reduce the burst release to about 10%, meaning that almost complete entrapment of the protein could be achieved. The release of IgG from degrading microspheres was predominantly dependent on the DS and the amount of encapsulated dextranase. No differences in release of IgG from microspheres with and without dextranase were observed at high DS (DS 13). This was ascribed to the inability of the enzyme to degrade these microspheres. On the other hand, the entrapped protein was completely released from enzymatically degrading microspheres with a DS 4. Moreover, the release rate of IgG was proportional to the degradation rate of these microspheres (depending on the amount of co-encapsulated dextranase). Interestingly, an almost zero-order release was observed from these microspheres for periods up to 30 days. (C) 1999 Published by Elsevier Science B.V. All rights reserved.