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

Abstract

Thermoresponsive polymers that undergo sol-gel transition in a physiological temperature range have been drawing attention for biomedical applications as drug delivery systems.Poloxamer P407 is commonly used as thermogelling material and has already been approved by the Food and Drug Administration (FDA) in licenced medicines. However, its solutions have 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 while retaining the thermogelling properties by either conjugating P407 with other polymers or introducing inter-micelle linkers to the poloxamer ends. However, chemical modifications can have several undesirable side-effects because 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 solution's formulations with additives including hydrophilic polymers (such as crosslinked polyacrylic acid, polyvinyl alcohol and polysaccharides) and nanoparticles. These additives have been used to enhance the P407 thermogel's properties. However, the majority of these studies fail to generate P407 gels with improved strength to the standard 20 % w/w solution used. This review investigates the approaches used to improve the properties of poloxamer 407 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.

Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation

“…Poloxamer 407 is an FDA-approved amphiphilic polymeric surfactant approved for oral, parenteral, and topical (vaginal, dermal, and ocular routes). 18 , 19 , 20 , 21 Poloxamer 407 is commonly used in various ocular formulations. Interestingly, Poloxamer 407-coated nanoparticles (NPs) of size ∼200 nm have shown the capability to penetrate through the mucin layer present at various mucosal surfaces including the eye.…”

Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives

“…However, P407 gels will be retained on the nail plate for a shorter period as compared to nail lacquer due to insufficient gel strength, weak stability and fast dissolution of the gels [ 16 ]. Drug loading capacity and gel strength of P407 gels may be improved either with the functional additives or by applying a chemical modification/conjugation approach [ 16 , 17 , 18 ]. Chemical modification and conjugation with crosslinker/polymers require costly and lengthy toxicity testing.…”