Berko Yvonne A, Akala Emmanuel O
Center for Drug Research and Development, Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street, NW, Washington, DC 20059, United States.
Pharm Nanotechnol. 2020;8(2):108-132. doi: 10.2174/2211738508666200224110410.
Combination chemotherapy capable of overcoming cancer drug resistance can be facilitated by nanotechnology.
Synthesis, characterization, statistical experimental design, analysis and optimization of stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneous delivery of paclitaxel and 17-AAG in breast cancer therapy were investigated.
An acetal crosslinker and a poly(ɛ)caprolactone macromonomer were synthesized and characterized. The statistical experimental design used was the response surface method (RSM). We used the central composite face-centered design (CCF) in three independent factors and seventeen runs. Nanoparticles were fabricated by dispersion polymerization techniques. Response variables evaluated were: particle size, drug loading, encapsulation efficiency, and in vitro availability.
Scanning electron micrographs showed the formation of spherical nanoparticles. Computer software was used for the analysis of variance with a 95% confidence level and Q2 (goodness of prediction) to select an appropriate model for each of the response variables. Each term in each of the models was tested for the significance of the regression coefficients. The computer software optimizer was used for optimization to select factor combination to minimize particle size, time (h) for maximum release of paclitaxel and 17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize paclitaxel and 17-AAG encapsulation efficiency.
The optimization was successful, as shown by the validation data which lie within the confidence intervals of predicted values of the response variables. The selected factor combination is suitable for the in vivo evaluation of the nanoparticles loaded with paclitaxel and 17-AAG.
纳米技术有助于研发出能够克服癌症耐药性的联合化疗方案。
研究用于乳腺癌治疗的隐形pH敏感聚合物纳米粒的合成、表征、统计实验设计、分析及优化，该纳米粒可作为同时递送紫杉醇和17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）的平台。
合成并表征了一种缩醛交联剂和一种聚己内酯大分子单体。所采用的统计实验设计为响应面法（RSM）。我们使用了包含三个独立因素和十七次运行的中心复合表面中心设计（CCF）。通过分散聚合技术制备纳米粒。评估的响应变量包括：粒径、载药量、包封率和体外释放度。
扫描电子显微镜照片显示形成了球形纳米粒。使用计算机软件在95%置信水平和Q2（预测优度）下进行方差分析，为每个响应变量选择合适的模型。对每个模型中的每一项进行回归系数显著性检验。使用计算机软件优化器进行优化，以选择能使粒径最小、使紫杉醇和17-AAG最大程度释放的时间（小时）、使紫杉醇和17-AAG载药效率最大化以及使紫杉醇和17-AAG包封率最大化的因素组合。
验证数据落在响应变量预测值的置信区间内，表明优化成功。所选因素组合适用于对负载紫杉醇和17-AAG的纳米粒进行体内评估。
