Mechanistic formation of drug-encapsulated Janus particles through emulsion solvent evaporation

Janus particles are emerging as structurally unique drug carriers with the potential to deliver multiple drugs and agents. Although synthesis methods have been extensively explored to fabricate Janus particles, it remains a challenge to generate drug-loaded Janus particles through an economical, high throughput technique. Here, we report the formation of the first drug-loaded, micro-scale Janus particles prepared using a single-step emulsion solvent evaporation approach. Our results revealed that both the net charge of drug molecules (i.e. glibenclamide, tolbutamine, rapamycin and lidocaine) and polymer weight ratio (i.e. poly(lactic-co-glycolic) and polycaprolactone) were critical in determining the formation of Janus particles. The formation of drug-loaded Janus particles was proven to be thermodynamically-driven in accordance to the classical equilibrium spreading coefficient theory, which is strongly governed by interfacial tensions. Specifically, comparable interfacial tensions between the two interacting polymers with the water phase were identified to be key criteria to achieve the Janus particles hemispheric structure. Such interfacial tensions were amenable, and were found to be highly dependent on the interfacial charge density attributed to both drug and polymer ratio. Hereby, this study provides a mechanistic insight into the fabrication of drug-loaded Janus particles and paves an important path towards large-scale production of Janus particles using a simplified, single-step emulsion solvent evaporation strategy.