Chitosan nanoparticle as protein delivery carrier - Systematic examination of fabrication conditions for efficient loading and release
Chitosan nanoparticle as protein delivery carrier - Systematic examination of fabrication conditions for efficient loading and release
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DOI：
10.1016/j.colsurfb.2007.04.009
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Gan, Quan;Wang, Tao
近年来，通过不同的制备工艺制备的壳聚糖纳米颗粒作为治疗性蛋白和基因的载体得到了广泛的研究，它们具有不同程度的有效性和缺陷。本工作旨在进一步探索多离子凝聚的制备工艺，以及相关的加工条件，在这些条件下，蛋白质的包封和随后的释放可以被系统地和可预测地操纵，从而获得预期的效果。以牛血清白蛋白为模型蛋白，以聚阴离子三聚磷酸酯（TPP）为凝聚交联剂，采用包封法或孵育法包封，形成壳聚糖-牛血清白蛋白-TPP纳米颗粒。对负载BSA的壳聚糖-TPP纳米颗粒的粒径、形貌、zeta电位、BSA包封效率和随后的释放动力学进行了表征，发现其主要取决于壳聚糖分子量、壳聚糖浓度、BSA负载浓度和壳聚糖/TPP质量比等因素。不同负载条件下制备的BSA纳米颗粒尺寸在200 ~ 580nm之间，具有较高的zeta电位。负载BSA颗粒的详细时序TEM成像显示了颗粒的膨胀和降解过程。由于表面蛋白质从亚层中解吸和扩散而释放的初始破裂与颗粒大小和形状的变化没有直接关系，这种变化仅在6小时后才非常明显。同样值得注意的是，后期颗粒降解和解体并没有产生实质性的后续释放，因为剩余的蛋白质分子具有适应性的3-D构象，可以与阳离子壳聚糖链紧密结合和纠缠。总的来说，本研究表明，多离子凝聚法制备蛋白质负载壳聚糖纳米粒子提供了简单的制备条件和一个清晰的处理窗口，可以操纵纳米粒子的物理化学性质（如大小和表面电荷），可以调节蛋白质的包封效率和随后的释放曲线。壳聚糖纳米粒子系统的缺点是在释放大量蛋白质分子时难以控制初始爆发效应。(C) 2007 Elsevier B.V.版权所有
Chitosan nanoparticles fabricated via different preparation protocols have been in recent years widely studied as carriers for therapeutic proteins and genes with varying degree of effectiveness and drawbacks. This work seeks to further explore the polyionic coacervation fabrication process, and associated processing conditions under which protein encapsulation and subsequent release can be systematically and predictably manipulated so as to obtain desired effectiveness. BSA was used as a model protein which was encapsulated by either incorporation or incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan-TPP nanoparticles were characterized for particle size, morphology, zeta potential, BSA encapsulation efficiency, and subsequent release kinetics, which were found predominantly dependent on the factors of chitosan molecular weight, chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio. The BSA loaded nanoparticles prepared under varying conditions were in the size range of 200-580 nm, and exhibit a high positive zeta potential. Detailed sequential time frame TEM imaging of morphological change of the BSA loaded particles showed a swelling and particle degradation process. Initial burst released due to surface protein desorption and diffusion from sublayers did not relate directly to change of particle size and shape, which was eminently apparent only after 6 h. It is also notable that later stage particle degradation and disintegration did not yield a substantial follow-on release, as the remaining protein molecules, with adaptable 3-D conformation, could be tightly bound and entangled with the cationic chitosan chains. In general, this study demonstrated that the polyionic coacervation process for fabricating protein loaded chitosan nanoparticles offers simple preparation conditions and a clear processing window for manipulation of physiochemical properties of the nanoparticles (e.g., size and surface charge), which can be conditioned to exert control over protein encapsulation efficiency and subsequent release profile. The weakness of the chitosan nanoparticle system lies typically with difficulties in controlling initial burst effect in releasing large quantities of protein molecules. (C) 2007 Elsevier B.V. All rights reserved.