The overall objective was to prepare a highly accurate nanocarrier system of mesalamine for the treatment of ulcerative colitis with increased therapeutic efficacy and targeting. In the formulation of nanocarrier systems, optimization is a critical process for understanding nanoformulation variables and quality aspects. The goal of the present work was to determine the effect of independent variables, i.e., the concentrations of chitosan, carboxymethyl inulin (CMI), and the drug on the response variables, i.e., particle size and percent entrapment efficiency of the mesalamine-loaded nanoparticle using the Box Behnken design (BBD). The correlation between the independent and dependent variables was investigated using the Design Expert generated mathematical equations, contour, and response surface designs. An optimized batch was developed using the ionotropic gel method with selected independent variables (A: + 1 level, B: 0 level, C: − 1 level) and the developed nanoparticles had a particle size of 184.18 nm, zeta potential 26.54 mV, and entrapment efficiency 88.58%. The observed responses were remarkably similar to the predicted values. The morphological studies revealed that the formulated nanoparticles were spherical, and the results of the FTIR and DSC studies indicated the drug-polymer compatibility. The nanoparticle showed less than 5% release in the pH 1.2. In the colonic region (pH 7.4), more than 80 % of the medication was released after 24 h. The kinetics study showed that the Higuchi and Korsemeyer-Peppas models had R2 values of 0.9426 and 0.9784 respectively, for the developed formulation indicating linearity, as revealed by the plots. This result justified the sustained release behavior of the formulation. The mesalamine-loaded chitosan-CMI nanoparticle has been successfully developed using the ionotropic gelation method. The nanoparticles developed in this study were proposed to deliver the drug to its desired site. The developed nanoparticles were likely to have a small particle size with positive zeta potential and high percent drug entrapment. It could be stated from the results that BBD can be an active way for optimizing the formulation and that nanoparticles can be a potential carrier for delivering therapeutics to the colon.

中文翻译：

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设计专家作为统计工具，使用 Box Behnken 因子设计优化负载 5-ASA 的基于生物聚合物的纳米粒子

总体目标是制备一种高度准确的美沙拉嗪纳米载体系统，用于治疗溃疡性结肠炎，提高治疗效果和靶向性。在纳米载体系统的配方中，优化是理解纳米配方变量和质量方面的关键过程。本工作的目标是确定自变量的影响，即壳聚糖、羧甲基菊粉 (CMI) 的浓度和药物对响应变量的影响，即负载美沙拉嗪的纳米颗粒的粒径和截留率百分比使用 Box Behnken 设计 (BBD)。使用设计专家生成的数学方程、等高线和响应面设计来研究自变量和因变量之间的相关性。使用具有选定自变量（A：+ 1 水平，B：0 水平，C：- 1 水平）的离子型凝胶方法开发了优化批次，开发的纳米颗粒的粒径为 184.18 nm，zeta 电位为 26.54 mV，和截留率 88.58%。观察到的反应与预测值非常相似。形态学研究表明，配制的纳米颗粒是球形的，FTIR 和 DSC 研究的结果表明药物与聚合物的相容性。纳米颗粒在 pH 1.2 中的释放量低于 5%。在结肠区域 (pH 7.4)，超过 80% 的药物在 24 小时后释放。动力学研究表明 Higuchi 和 Korsemeyer-Peppas 模型的 R2 值分别为 0.9426 和 0.9784，对于开发的配方，表明线性，如绘图所示。该结果证明了制剂的缓释行为。使用离子型凝胶法成功开发了负载美沙拉嗪的壳聚糖-CMI 纳米颗粒。在这项研究中开发的纳米粒子被提议将药物输送到其所需的部位。开发的纳米粒子可能具有小粒径，具有正 zeta 电位和高百分比的药物截留率。从结果可以看出，BBD 可以成为优化配方的积极方式，纳米颗粒可以成为向结肠输送治疗剂的潜在载体。在这项研究中开发的纳米粒子被提议将药物输送到其所需的部位。开发的纳米颗粒可能具有小粒径，具有正 zeta 电位和高百分比的药物截留率。从结果可以看出，BBD 可以成为优化配方的积极方式，纳米颗粒可以成为向结肠输送治疗剂的潜在载体。在这项研究中开发的纳米颗粒被提议将药物输送到其所需的部位。开发的纳米粒子可能具有小粒径，具有正 zeta 电位和高百分比的药物截留率。从结果可以看出，BBD 可以成为优化配方的积极方式，纳米颗粒可以成为向结肠输送治疗剂的潜在载体。