Polymeric nanoparticles have significant potential to improve the therapeutic efficacy of drugs by providing superior protection and facilitating delivery at specific target sites. While there have been some significant successes in this field, there are still limited examples of polymeric materials in clinical applications. One of the challenges with translating nanoparticles to clinical use is the many biological roadblocks that prevent successful delivery,1 thus there remains a need to design smarter materials to migrate these barriers. It is also challenging to upscale polymer formulations as they are commonly designed using multi-step syntheses or under high dilution.1
Herein, we discuss the development of new stimuli-responsive delivery systems based on combining responsive functionality with synthesis strategies that are attractive for scale-up, including emulsion and PISA. We have demonstrated the design of pH responsive emulsion nanoparticles that can be tuned to disassemble or swell in response to pH. These systems showed different biological interactions, such as toxicity and endosomal escape, based on tuning their stimuli-responsive properties. We also showed the use of ethyl lipoate to synthesise degradable PISA formulations including 10-30% ethyl lipoate. These nanoparticles were shown to degrade in the presence of reducing agent. These studies indicate the potential of stimuli-responsive nanoparticles to be tuned to control degradability and biological interactions and thus provide useful delivery systems for the future.