This study investigated the effects of additives on the properties of poloxamer (P) 407 thermogels, employing a design-of-experiments (DoE) approach. P407 is a thermoresponsive triblock copolymer that exhibits a solution to gel transition at a critical temperature, typically between 15-25 °C, dependant on polymer concentration. This thermoresponsive gelation has made P407 attractive for many applications including drug delivery, cell culture and tissue engineering. However, the gels formed do not have sufficient strength for some applications where the materials will be exposed to shear, such as topical drug delivery. There have been attempts to improve P407 thermogel properties by the addition of other hydrophilic polymers. However, these studies were limited to a small number of polymers, typically in binary mixtures, exploring one variable at a time. In this study, a DoE approach was carried out using a two-level model exploring P407, P188, poly(vinyl alcohol), poly(ethylene glycol), and poly(acrylic acid) as variables, including an exploration of molecular weight of the latter three additives. The variables were given two different levels (concentrations) to generate a total of 16 training formulations. The thermoresponsive gelation of these 16 formulations was studied by rheometry and predictive models built for gel strength (G’) and gelation temperature (Tgel) responses. The model was able to predict the thermoresponsive gelation of complex octonary test blends, significantly streamlining formulation development processes relative to current methods. The model was then able to identify novel thermoresponsive gel formulations with 20 % improved gel strength compared to a standard 20 % P407 solution, which may be used as temperature-responsive materials for advanced healthcare applications.

中文翻译：

---

从复杂的聚合物混合物开发热敏胶凝剂的实验设计方法

这项研究采用实验设计（DoE）方法研究了添加剂对泊洛沙姆（P）407热凝胶性能的影响。P407是一种热响应性三嵌段共聚物，根据聚合物浓度的不同，在临界温度（通常为15-25°C）下，溶液会呈现出凝胶转变的状态。这种热敏性胶凝作用使P407吸引了许多应用，包括药物递送，细胞培养和组织工程。然而，所形成的凝胶对于材料将要经受剪切的某些应用（例如局部药物递送）没有足够的强度。已经尝试通过添加其他亲水性聚合物来改善P407热凝胶性质。但是，这些研究仅限于少量聚合物，通常为二元混合物，一次探索一个变量。在这项研究中，DoE方法是使用两级模型进行探索的，该模型以P407，P188，聚乙烯醇，聚乙二醇和聚丙烯酸为变量，其中包括对P407，P188，聚乙二醇和聚丙烯酸的探索。后三种添加剂。给变量两个不同的水平（浓度），以生成总共16种训练公式。通过流变学和针对凝胶强度（G'）和凝胶温度（Tgel）响应建立的预测模型研究了这16种配方的热响应凝胶化。该模型能够预测复杂的辛酸测试混合物的热响应胶凝性，与当前方法相比，显着简化了制剂开发过程。