Institute of Materials Research and Engineering, Agency for Science, Technology and Research, 3 Research Link, Singapore 117602, Singapore.
Biomacromolecules. 2010 May 10;11(5):1241-7. doi: 10.1021/bm901450r.
The development of polyelectrolyte multilayer microcapsules as a delivery system containing bioactive compounds strongly depends on understanding of the major factors that influence capsules' loading and release of incorporated substances. Mechanism of protein release from biocompatible polyelectrolyte multilayer microcapsules has been examined using two different approaches of protein encapsulation: (i) "preloading" via coprecipitation of tetramethylrhodamine isothiocyanate (TRITC)-labeled bovine serum albumin (BSA) (TRITC-BSA) into CaCO(3) particles followed by multilayer assembly and (ii) "postloading" of TRITC-BSA in preformed empty capsules templated on pure CaCO(3) particles taken in the same amount as in "preloading" approach. Polysaccharides (alginate (Alg) or dextran sulfate (Dex)) and polyarginine (PAr) were used as layer constituents. On the basis of the effects of capsule shell composition and thickness, method of protein encapsulation, volume of the surrounding medium, and frequency of medium refreshment on protein release profile, we reveal a mechanism of protein release. The key phenomenon determining the protein release is the property of multilayer polyelectrolyte shells relating to the entrapping and accumulation of protein molecules. The results obtained together with the suggested mechanism of capsule loading and protein release allow us to propose the use of polyelectrolyte microcapsules as a depot system to supply and maintain a defined level of macromolecular drug concentration in surrounding medium.
聚电解质多层微胶囊作为含有生物活性化合物的递送系统的发展强烈依赖于对影响胶囊包封和释放所包含物质的主要因素的理解。使用两种不同的蛋白质包封方法(i)通过共沉淀将四甲基罗丹明异硫氰酸酯(TRITC)标记的牛血清白蛋白(BSA)(TRITC-BSA)预加载到 CaCO3 颗粒中,然后进行多层组装和(ii)在预先形成的空胶囊中“后加载”TRITC-BSA 在纯 CaCO3 颗粒上模板化,其数量与“预加载”方法相同。多糖(藻酸盐(Alg)或硫酸葡聚糖(Dex))和聚精氨酸(PAr)用作层组成部分。基于胶囊壳组成和厚度、蛋白质包封方法、周围介质体积和介质更新频率对蛋白质释放曲线的影响,我们揭示了蛋白质释放的机制。决定蛋白质释放的关键现象是与蛋白质分子包封和积累有关的多层聚电解质壳的性质。获得的结果以及提出的胶囊加载和蛋白质释放机制允许我们提出使用聚电解质微胶囊作为储存系统,以在周围介质中供应和维持大分子药物浓度的定义水平。