Factorial Design Based Multivariate Modeling and Optimization of Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)-diaminohexane) Polymeric Matrix Based Nanocarriers.
Factorial Design Based Multivariate Modeling and Optimization of Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)-diaminohexane) Polymeric Matrix Based Nanocarriers.
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基于析因设计的可调谐生物响应精氨酸接枝聚（胱胺双（丙烯酰胺）-二氨基己烷）聚合物基质纳米载体的多变量建模和优化。
DOI：
10.1021/acs.molpharmaceut.6b00861
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发表时间：
2017
影响因子：
4.9
通讯作者：
Chougule,MahavirB
中科院分区：
文献类型：
--
作者：
Yang,Rongbing;Nam,Kihoon;Kim,SungWan;Turkson,James;Zou,Ye;Zuo,YiY;Haware,RahulV;Chougule,MahavirB
纳米载体所需的特性对于探索其治疗潜力至关重要。本研究旨在开发可调的生物响应性新合成的独特的精氨酸接枝聚（胱胺双（丙烯酰胺）-己二胺）[ABP]聚合物基质为基础的纳米载体，通过使用L9田口因子设计，期望函数，和多变量方法。选定的处方和工艺参数为ABP浓度、丙酮浓度、丙酮与ABP溶液的体积比和药物浓度。所测量的纳米载体特性是粒径、多分散指数、ζ电位和载药量百分比。从最初开发的预测模型计算的纳米载体特征的实验验证显示无显著差异（p> 0.05）。基于多变量建模的负载有亲水性对乙酰氨基酚的<100 nm的优化的阳离子纳米载体制剂重新适应于疏水性依托泊苷负载，除了负载百分比提高之外没有显著变化（p> 0.05）。这是第一个研究重点是ABP聚合物基质为基础的纳米载体的发展。纳米载体粒度在PBS 7.4中稳定48小时。与生理pH相比，在较低pH 6.4下zeta电位的增加显示了可能的内体逃逸能力。谷胱甘肽在生理条件下的触发释放表明了生物响应性纳米载体的细胞溶质靶向递送负载药物的能力。总之，这种独特的系统方法提供了合理的评估和预测的可调生物响应ABP为基础的基质纳米载体，这是建立在选定的有限数量的智能实验。
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.
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影响因子：
14
作者：
Kihoon Nam;Hye Yeong Nam;Kim, Pyung-Hwan;Kim, Sung Wan
通讯作者：
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影响因子：
4.6
作者：
Patel, Apurva R.;Spencer, Shawn D.;Chougule, Mahavir B.;Safe, Stephen;Singh, Mandip
通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
4.7
作者：
Ou, Mei;Wang, Xu-Li;Kim, Sung Wan
通讯作者：
Kim, Sung Wan
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影响因子：
--
作者：
Susanne R. Youngren;R. Tekade;B. Gustilo;P. Hoffmann;M. Chougule
通讯作者：
M. Chougule