Yang Rongbing, Nam Kihoon, Kim Sung Wan, Turkson James, Zou Ye, Zuo Yi Y, Haware Rahul V, Chougule Mahavir B
Translational Drug and Gene Delivery Research (TransDGDR) Laboratory, Department of Pharmaceutical Sciences, Department of Pharmaceutics and Drug Delivery, Research of Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi , University, Mississippi 38677, United States.
Translational Drug Delivery Research (TransDDR) Laboratory, Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo , Hilo, Hawaii 96720, United States.
Mol Pharm. 2017 Jan 3;14(1):252-263. doi: 10.1021/acs.molpharmaceut.6b00861. Epub 2016 Nov 29.
Desired characteristics of nanocarriers are crucial to explore its therapeutic potential. This investigation aimed to develop tunable bioresponsive newly synthesized unique arginine grafted poly(cystaminebis(acrylamide)-diaminohexane) [ABP] polymeric matrix based nanocarriers by using L9 Taguchi factorial design, desirability function, and multivariate method. The selected formulation and process parameters were ABP concentration, acetone concentration, the volume ratio of acetone to ABP solution, and drug concentration. The measured nanocarrier characteristics were particle size, polydispersity index, zeta potential, and percentage drug loading. Experimental validation of nanocarrier characteristics computed from initially developed predictive model showed nonsignificant differences (p > 0.05). The multivariate modeling based optimized cationic nanocarrier formulation of <100 nm loaded with hydrophilic acetaminophen was readapted for a hydrophobic etoposide loading without significant changes (p > 0.05) except for improved loading percentage. This is the first study focusing on ABP polymeric matrix based nanocarrier development. Nanocarrier particle size was stable in PBS 7.4 for 48 h. The increase of zeta potential at lower pH 6.4, compared to the physiological pH, showed possible endosomal escape capability. The glutathione triggered release at the physiological conditions indicated the competence of cytosolic targeting delivery of the loaded drug from bioresponsive nanocarriers. In conclusion, this unique systematic approach provides rational evaluation and prediction of a tunable bioresponsive ABP based matrix nanocarrier, which was built on selected limited number of smart experimentation.
纳米载体的理想特性对于探索其治疗潜力至关重要。本研究旨在通过使用L9田口因子设计、合意性函数和多变量方法，开发基于新合成的独特的精氨酸接枝聚（胱胺双（丙烯酰胺）-二氨基己烷）[ABP]聚合物基质的可调谐生物响应性纳米载体。所选的配方和工艺参数为ABP浓度、丙酮浓度、丙酮与ABP溶液的体积比以及药物浓度。所测量的纳米载体特性为粒径、多分散指数、zeta电位和载药百分比。根据最初开发的预测模型计算出的纳米载体特性的实验验证显示无显著差异（p>0.05）。基于多变量建模优化的负载亲水性对乙酰氨基酚的<100 nm阳离子纳米载体制剂，在负载疏水性依托泊苷时进行了重新调整，除了载药百分比提高外，无显著变化（p>0.05）。这是第一项专注于基于ABP聚合物基质的纳米载体开发的研究。纳米载体粒径在PBS 7.4中48小时内稳定。与生理pH相比，在较低pH 6.4时zeta电位的增加表明可能具有内体逃逸能力。谷胱甘肽在生理条件下触发释放，表明生物响应性纳米载体具有将负载药物靶向递送至细胞质的能力。总之，这种独特的系统方法为基于可调谐生物响应性ABP的基质纳米载体提供了合理的评估和预测，该纳米载体基于选定的有限数量的智能实验构建。
