Gan Quan, Wang Tao, Cochrane Colette, McCarron Paul
School of Chemical Engineering, Queen's University Belfast, Belfast BT9 5AG, UK.
Colloids Surf B Biointerfaces. 2005 Aug;44(2-3):65-73. doi: 10.1016/j.colsurfb.2005.06.001.
This work investigates the polyanion initiated gelation process in fabricating chitosan-TPP (tripolyphosphate) nanoparticles in the size range of 100-250 nm intended to be used as carriers for the delivery of gene or protein macromolecules. It demonstrates that ionic gelation of cationic chitosan molecules offers a flexible and easily controllable process for systematically and predictably manipulating particle size and surface charge which are important properties in determining gene transfection efficacy if the nanoparticles are used as non-viral vectors for gene delivery, or as delivery carriers for protein molecules. Variations in chitosan molecular weight, chitosan concentration, chitosan to TPP weight ratio and solution pH value were examined systematically for their effects on nanoparticle size, intensity of surface charge, and tendency of particle aggregation so as to enable speedy fabrication of chitosan nanoparticles with predetermined properties. The chitosan-TPP nanoparticles exhibited a high positive surface charge across a wide pH range, and the isoelectric point (IEP) of the nanoparticles was found to be at pH 9.0. Detailed imaging analysis of the particle morphology revealed that the nanoparticles possess typical shapes of polyhedrons (e.g., pentagon and hexagon), indicating a similar crystallisation mechanism during the particle formation and growth process. This study demonstrates that systematic design and modulation of the surface charge and particle size of chitosan-TPP nanoparticles can be readily achieved with the right control of critical processing parameters, especially the chitosan to TPP weight ratio.
本研究探讨了在制备尺寸范围为100 - 250 nm的壳聚糖-三聚磷酸钠（TPP）纳米颗粒时，聚阴离子引发的凝胶化过程，这些纳米颗粒旨在用作基因或蛋白质大分子递送的载体。研究表明，阳离子壳聚糖分子的离子凝胶化提供了一个灵活且易于控制的过程，可用于系统地、可预测地控制粒径和表面电荷，而如果将纳米颗粒用作基因递送的非病毒载体或蛋白质分子的递送载体，粒径和表面电荷是决定基因转染效率的重要特性。系统研究了壳聚糖分子量、壳聚糖浓度、壳聚糖与TPP的重量比以及溶液pH值对纳米颗粒大小、表面电荷强度和颗粒聚集趋势的影响，以便能够快速制备具有预定特性的壳聚糖纳米颗粒。壳聚糖-TPP纳米颗粒在较宽的pH范围内表现出高正表面电荷，并且发现纳米颗粒的等电点（IEP）为pH 9.0。对颗粒形态的详细成像分析表明，纳米颗粒具有典型的多面体形状（如五边形和六边形），这表明在颗粒形成和生长过程中存在类似的结晶机制。本研究表明，通过正确控制关键工艺参数，特别是壳聚糖与TPP的重量比，可以很容易地实现壳聚糖-TPP纳米颗粒表面电荷和粒径的系统设计和调节。
