基于Box-Behnken设计的载姜黄素海藻酸钙微球结肠直肠癌的优化及体外评价

Amit Kumar Pandey, Udai Vir Singh Sara, Harinath Dwivedi
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摘要

背景与目的:在肺癌和乳腺癌之后,结直肠癌(CRC)是第三大最常见的癌症类型,死亡率第二高。姜黄素就是这样一种天然存在的膳食化合物,被证明有治疗结肠癌的希望。为此,本研究的目标是将Eudragit S100涂覆姜黄素,以治疗远端肠释放的结直肠癌。多颗粒剂型可增加姜黄素在结肠环境中的溶解度,维持药物释放,防止药物在结肠环境中突然降解。所有这些改变都可以提高结肠组织的水平,特别是在患者的结肠癌细胞中,从而可以提高治疗的效用。方法:采用离子化胶凝技术进行配方制备。此外,Design Expert 13在这项工作中使用了三因素,三水平的Box-Behnken设计(BBD)来优化结肠靶向给药的配方。以海藻酸钾浓度、氯化钙浓度和固化时间为自变量,对制备的微球进行细化,研究其对包埋效果和粒径的影响。将Eudragit S100肠溶包被在改良型海藻酸钙珠上。结果:聚合物的浓度和固化时间分别对粒径和包埋效果有较大影响。氯化钙和海藻酸钾的理想浓度分别为15% w/v和6% w/v,固化时间为20分钟。改进后的药物包封率为88.4%,颗粒尺寸为708 μm。经优化的海藻酸钙微珠肠溶后12小时,79.23±0.32%的药物释放(增重10%)。结论:本研究最终证明了Box-Behnken设计在冒号靶向制剂优化中的有效性。为了有效治疗结直肠癌,可以口服肠包被海藻酸钙微珠,将姜黄素精确地输送到结肠。
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Optimization and In Vitro Evaluation of Curcumin-loaded Calcium Alginate Microbeads using Box-Behnken Design for Colorectal Cancer
After lung cancer and breast cancer, colorectal cancer (CRC) is the third most common type of cancer and has the second-highest fatality rate. Curcumin is one such naturally occurring dietary compound that demonstrated promise to treat colon cancer. For that, the goal of the current study was to coat curcumin with Eudragit S100 to treat colorectal cancer in the distal intestine release. The multiparticulate dosage form can increase the solubility of curcumin in the colon environment, sustain the drug release, and protect the drug from abrupt degradation in the colon environment. All of these alterations can enhance the colon tissue levels, especially in the colon cancer cells in the patients, and thereby can enhance the utility of the therapy. By using the ionotropic gelation technique, the formulations were made. Moreover, Design Expert 13 used a three-factor, three-level Box-Behnken design (BBD) in this work to optimize the formulation for colon-targeted drug delivery. The concentration of potassium alginate, the concentration of calcium chloride, and the curing duration were considered independent variables, and prepared microbeads were refined to study their impacts on entrapment effectiveness and particle size. Eudragit S100 was enteric coated on Calcium alginate beads with an improved core. Regarding particle size and entrapment effectiveness, respectively, the polymer concentration and curing duration had a substantial impact. The ideal concentrations of calcium chloride and potassium alginate were 15% w/v and 6% w/v, respectively, with a 20-minute curing time. With a drug entrapment efficiency of 88.4%, the improved formulation had particles with a size of 708 μm. After 12 hours, 79.23±0.32% of the drug was released following an enteric coating of Eudragit S100 of optimized calcium alginate microbeads (10% weight gain). The present study conclusively demonstrates the usefulness of a Box-Behnken design in the optimization of colon-targeted formulations. To effectively treat colorectal cancer, enteric-coated calcium alginate microbeads can be administered orally to deliver curcumin precisely to the colon.
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