Chitosan and hyaluronan coated liposomes for pulmonary administration of curcumin

Aiming at improving the nebulization performances and lung antioxidant protection of curcumin, chitosan or hyaluronan-coated liposomes were prepared and their characteristics and performances were compared with that of uncoated liposomes. Curcumin loaded liposomes displayed a diameter lower than 100 nm, the coating with both polymers led to a small increase of vesicle size around 130 nm and the zeta potential turned to positive values using chitosan while remained negative using hyaluronan. Chitosan allowed the formation of more lamellar and stiffer vesicles with a higher bilayer thickness (dB ∼ 59 Ǻ) with respect to the uncoated liposomes, whereas hyaluronan allowed the interdigitation of the bilayers (dB ∼ 47 Ǻ) due to the polymer intercalation between phospholipid head groups resulting in vesicles mainly organized in uncorrelated bilayers. Both polymer coatings, especially hyaluronan, greatly improved the stability of the vesicles, especially during the nebulization process, promoting the deposition of the phytodrug in the furthest stages of the impactor in high amount (≥50%). Polymer coated vesicles were biocompatible and improved the curcumin ability to protect A549 cells from the oxidative stress induced by hydrogen peroxide, restoring healthy conditions (cell relative metabolic activity 100%). In particular, a synergic effect of curcumin and hyaluronan was observed resulting in a proliferative effect and a subsequent further enhancement of cell relative metabolic activity up to 120%.