Supercritical CO2 engineered niosomes as functional materials for oral drug delivery

Achieving scalable and controlled production of nanovesicles remains a major bottleneck in translating nanocarrier systems to industry. Conventional batch methods, such as thin-film hydration and ethanol injection, often show low reproducibility, residual solvents, and multistep workflows that hinder scale-up. To address these challenges, we developed SuperSomes, a supercritical CO 2 (SC-CO 2 )–based process enabling continuous, solvent-free fabrication of nanovesicles. The method relies on atomization of an aqueous phase within a gas-expanded medium, promoting rapid self-assembly of surfactant or lipid molecules under mild conditions and allowing precise control over vesicle size and composition. As a proof of concept, we used SuperSomes to generate Span 80/Tween 80 or Span 80/Capric acid (C10) niosomes for oral drug delivery. By systematically tuning surfactant ratios, we identified how hydrophilic–lipophilic balance and packing parameters govern vesicle formation and stability. The resulting niosomes showed high resistance to pH and temperature variations. In vitro Caco-2 studies revealed enhanced intracellular uptake and paracellular transport, indicating a dual absorption mechanism. In vivo , orally administered fluorescent niosomes exhibited minimal gastric retention and improved intestinal permeation. Overall, SuperSomes offers a reproducible, scalable, and environmentally friendly platform for producing nanocarriers tailored for oral delivery, overcoming key limitations of conventional manufacturing approaches.