A Design-of-Experiments Approach to Developing Thermoresponsive Gelators From Complex Polymer Mixtures

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.