Optimization of quercetin: liposomal dry powders for pulmonary delivery using supercritical CO₂-assisted spray drying

Quercetin exhibits anti-inflammatory and antioxidant properties. Incorporating quercetin into liposomes can overcome its limited water solubility and poor oral bioavailability, making it a promising candidate for treating inflammatory diseases. For pulmonary administration, supercritical CO2-assisted spray drying can be used to convert liposomal suspensions into dry powder formulations suitable for inhalation. However, the extraction power of scCO2 can pose challenges on retaining the incorporation efficiency (IE) of this flavonoid in the lipid bilayer. This study focuses on optimizing quercetin's IE after drying using different liposomal lipid compositions with varying surface charges. The IE of quercetin into positively charged liposomes was 57 %. Additionally, the resulting powders had a mass median aerodynamic diameter of 1.7 µm and a fine particle fraction (particle size < 5 µm) of 63 %, indicating their suitability for inhalation. Cytotoxicity assays also revealed that both reconstituted liposomes and dry powder formulations were non-toxic to areolar fibroblast cells.