壳聚糖-三磷酸(TPP)纳米凝胶是研究广泛的药物传递载体系统,通常通过简单的混合过程制备。然而,加工因素对纳米凝胶生产的影响尚未得到广泛的探索,尽管理解和标准化这些因素以允许升级和商业用途的重要性。本研究旨在使用实验设计方法系统地评估各种制造和加工因素对纳米凝胶性能的影响。水动力尺寸,多分散指数(PDI),zeta电位,和包封效率被确定为依赖因素。温度,搅拌速率,壳聚糖级,交联剂的选择,温度和壳聚糖等级之间的相互作用项被发现对粒径有显著影响,而温度和交联剂的添加速率对PDI的影响也是值得注意的。此外,发现交联剂的添加速率和反应容器的体积影响包封效率。发现纳米凝胶的ζ电位受壳聚糖等级控制。开发中等分子量壳聚糖和TPP纳米凝胶的最佳制造条件包括:TPP溶液的添加速率设定为2mL/min,然后在50°C的温度和600rpm的搅拌速度下搅拌溶液。所用玻璃小瓶的体积为28mL,而搅拌器尺寸为20mm。该研究的第二个目的是评估扩大纳米凝胶的潜力。发现尺寸和PDI分别从128nm增加到151nm和从0.232增加到0.267,当反应混合物的体积从4毫升增加到20毫升时,其他处理因素保持不变。这些结果表明,当按比例放大时需要小心,因为纳米凝胶的性质可能随着生产规模的增加而显著改变。
Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the processing factors on nanogel production have not been extensively explored, despite the importance of understanding and standardising such factors to allow upscaling and commercial usage. This study aims to systematically evaluate the effects of various fabrication and processing factors on the properties of nanogels using a Design of Experiment approach. Hydrodynamic size, polydispersity index (PDI), zeta potential, and encapsulation efficiency were determined as the dependent factors. The temperature, stirring rate, chitosan grade, crosslinker choice, and the interaction term between temperature and chitosan grade were found to have a significant effect on the particle size, whereas the effect of temperature and the addition rate of crosslinker on the PDI was also noteworthy. Moreover, the addition rate of the crosslinker and the volume of the reaction vessel were found to impact the encapsulation efficiency. The zeta potential of the nanogels was found to be governed by the chitosan grade. The optimal fabrication conditions for the development of medium molecular weight chitosan and TPP nanogels included the following: the addition rate for TPP solution was set at 2 mL/min, while the solution was then stirred at a temperature of 50 °C and a stirring speed of 600 rpm. The volume of the glass vial used was 28 mL, while the stirrer size was 20 mm. The second aim of the study was to evaluate the potential for scaling up the nanogels. Size and PDI were found to increase from 128 nm to 151 nm and from 0.232 to 0.267, respectively, when the volume of the reaction mixture was increased from 4 to 20 mL and other processing factors were kept unchanged. These results indicate that caution is required when scaling up as the nanogel properties may be significantly altered with an increasing production scale.