Modifying the Properties of Thermogelling Poloxamer 407 Solutions through Covalent Modification and the Use of Polymer Additives

Thermoresponsive polymers that undergo sol-gel transition in a physiological temperature range have applications in biomedical science. Poloxamer 407 (P407) is commonly used as thermogelling material and has been approved by the Food and Drug Administration (FDA) in licenced medicines. However, it has significant drawbacks which limit its performance, particularly in drug delivery systems. In order to improve these properties, the chemical structure of P407 has been modified to produce stronger gels by either conjugating P407 with other polymers or introducing inter-micelle linkers to the terminal hydroxyl groups of P407. However, chemical modifications have several undesirable side-effects. The change in the chemical structure makes the polymer a novel excipient, and additional safety risks are possible, requiring expensive and time-consuming toxicity testing prior to regulatory approval. An alternative approach to covalent modification is modifying the P407 formulations with additives including hydrophilic polymers and nanoparticles, in an attempt to improve the properties of these materials. This review investigates the approaches used to modify the properties of P407 thermogelling materials, including the use of polymer additives and covalent modification. Several recommendations are made, based on efficacy and consideration of regulatory risk to guide the development of these materials toward use in real clinical applications.