Cu, Zn- Superoxide dismutase liposomal dry powder formulations production using supercritical CO2-assisted spray-drying: A proof-of-concept

Enzyme-based inhalable therapeutics for lung inflammation are gaining interest as an alternative to long-term corticosteroids treatments. However, enzymes have poor pharmacokinetics. Encapsulating enzymes in liposomes can increase their half-live and modify their biodistribution. But both liposomes and enzymes are susceptible to destabilization during storage. This drawback can be surpassed, by converting liposomal suspension into solid dosage forms for different administration routes, including inhalation. In this study, Cu, Zn- superoxide dismutase (SOD) was encapsulated in liposomes, then dried using supercritical CO₂-assisted spray-drying to make SOD-loaded liposomal dry powder formulations (SOD_Lip-DPFs). Upon resuspension in water, liposomes maintained structural integrity, with 99% SOD encapsulation efficiency and preserved enzymatic activity. Stability studies showed that SOD_Lip-DPFs maintained liposomal and enzyme stability for 50 days at 40% relative humidity. This offers a stable and efficient delivery system for enzyme-based inhalable therapeutics.