Thermoresponsive engineered emulsions stabilised with branched copolymer surfactants for nasal drug delivery of molecular therapeutics

Abstract

Novel branched copolymer surfactants (BCS) allow the formation of oil-in-water emulsions that exhibit a temperature-induced liquid-to-gel transition. If the temperature of this transition is between room and body temperature (ca 25 and 37 °C, respectively), then the emulsions form a gel in situ upon contact with the body. A major advantage of this in situ gelation is the potential to manipulate the materials at room temperature in the low viscosity liquid state, then administer them to the body to initiate a switch to a retentive gel state, which could be used to deliver drugs to challenging sites such as the nasal mucosa. There are, however, several important factors which have not been explored for thermoresponsive BCS-stabilised emulsions to progress their use towards this application. Neither the delivery of drugs from the materials, the retention on tissue, nor the impact of co-formulated drugs on the thermoresponsive behaviours, are known. Furthermore, it has not been demonstrated that the materials are compatible with devices to generate sprays of the correct profiles for nasal administration. In this study we investigate the potential of thermoresponsive BCS-stabilised emulsions for the nasal delivery of licensed molecular therapeutics to examine the potential of BCS emulsion systems as a carrier for medicines. It was found that thermoresponsive behaviours can be maintained in the presence of drug substances, and that the liberation of the incorporated drugs occurs in a sustained manner. The BCS appear to have comparable cytotoxicity to common excipients and significantly enhanced retention on nasal tissue compared to even well-established mucoadhesives. The emulsions were incorporated into a spray device to demonstrate that the materials can be atomised with a plume appropriate for nasal administration prior to in situ gelation.