Hyaluronan-cholesterol core–shell glycerosomes: innovative nanocarriers for mitigating smoke-induced oxidative stress and inflammation in the lungs

Lungs are constantly exposed to environmental stressors, such as cigarette smoke, which can lead to oxidative stress and inflammation, contributing to the development of chronic lung diseases. To mitigate these conditions, innovative lipid-based nanocarriers, including conventional and core–shell liposomes and glycerosomes, were developed and compared for lung delivery. Curcumin was selected as a potent antioxidant and encapsulated with high yields (> 70%) in the formulated systems. All the nanocarriers were eco-friendly produced by direct sonication, avoiding the use of organic solvents. The core–shell counterparts incorporated a hyaluronan-cholesterol shell without impacting size or polydispersity index, making them suitable for pulmonary administration. Aerosolization studies highlighted conventional and 25 core–shell glycerosomes as the most promising formulations due to their superior nebulization (delivered fraction >95%, fine particle dose >3800 μg, and MMAD values <4.2 μm, ideal for lung targeting). Biocompatibility assessments on A549 and 16HBE cell lines demonstrated good tolerability (cell viability >80%) at non-cytotoxic curcumin concentrations (<20 μM). Moreover, they effectively countered reactive oxygen species production in A549 cells (cell viability >90% after oxidative stress) and mitigated cigarette smoke extract-induced inflammation in 16HBE cells, outperforming free curcumin (pro-inflammatory IL-6 and IL-8 levels were significantly reduced to even below control levels). These findings suggest the potential of curcumin-loaded conventional and core–shell 25 glycerosomes as inhalable drug delivery systems for the treatment of oxidative stress and inflammation associated with smoke exposure.