Pickering emulsions for stimuli-responsive transdermal drug delivery: effect of rheology and microstructure on performance

Abstract

This work investigates the design of stimuli-responsive Pickering emulsions (PEs) for transdermal drug delivery applications, by exploring the impact of stabilising microgels size and interactions on their rheological and release properties. Temperature-responsive poly(N-isopropylacrylamide) microgels modified with 1-benzyl-3-vinylimidazolium bromide (pNIPAM-co-BVI) are synthesized in varying sizes and used to stabilise jojoba oil-in-water concentrated emulsions. The results reveals two distinct behaviours: for small microgels (∼300 nm), the PEs exhibit a smooth, uniform structure characterised by a mild yield stress, characteristic of soft glassy systems. Conversely, larger microgels (∼800 nm) induce droplet clustering, resulting in increased elasticity and a more complex yielding process. Interestingly, transdermal delivery tests demonstrate that microstructure, rather than bulk rheology, governs sustained drug release. The release process can be modelled as diffusion-controlled transport through a porous medium with random traps. At room temperature, the trap size corresponds to the droplet size, and the release time scales with the total dispersed phases volume fraction. However, at physiological temperature (37 °C), above the volume-phase transition temperature of the microgels, the release time increases significantly. The trap size approaches the microgel size, suggesting that microgel porosity becomes the dominant factor controlling drug release. Overall, the results highlight the critical role of microstructure design in optimising stimuli-responsive PEs for controlled transdermal drug delivery.