Uniform Microscale Thermoresponsive Liposomes for Controlled Release Above Body Temperature

Stimuli-responsive delivery systems, particularly thermoresponsive platforms, are becoming increasingly important for physiological applications, but their development has been limited by poor biocompatibility, slow response, and non-scalable fabrication methods. Liposomes offer a biocompatible and adaptable foundation for this need, but no scalable approach exists to produce uniform thermosensitive liposomes that activate above 37°C. Here, we present the first scalable strategy for generating monodisperse thermoresponsive liposomes using a corona-discharge- treated PDMS double-emulsion device. Aqueous cargo-containing cores are encapsulated within DPPC-containing oleic acid shells, with Pluronic F-127 added to the outer phase to stabilize the interface. Ethanol-mediated solvent extraction transforms these shells into lipid bilayers, and the combined use of rotational mixing and surfactant-assisted interfacial tuning reduces extraction time by more than 50% compared with prior reports while ensuring complete bilayer formation, even for thick shells. Under regulated extraction, droplets with thin lipid membranes incorporating Pluronic F-127 undergo abrupt rupture and cargo release at ∼41°C-45°C, providing stable encapsulation at physiological temperature and sharp thermally triggered release above body temperature. Overall, this work creates the first platform capable of producing uniform thermoresponsive liposomes that undergo abrupt, super-physiological temperature-triggered release, providing broad potential for drug delivery, biosensing, and synthetic biology.