Inhalable polymer-glycerosomes as safe and effective carriers for rifampicin delivery to the lungs

• Rifampicin was loaded in glycerosomes and polymer-glycerosomes (P-G).
• P-G were made adding trimethyl chitosan chloride or sodium hyaluronate to glycerosomes.
• An environmentally-friendly method was used to obtain polymer-glycerosomes.
• Polymer-glycerosomes provided a high rifampicin deposition in the lungs.
• Rifampicin vesicles were biocompatible and improved drug activity against the S. aureus.

Rifampicin loaded glycerosomes, vesicles composed of phospholipids, glycerol and water, were combined with trimethyl chitosan chloride (TMC) to prepare TMC-glycerosomes or, alternatively, with sodium hyaluronate (HY) to obtain HY-glycerosomes. These new hybrid nanovesicles were tested as carriers for pulmonary delivery of rifampicin. Glycerosomes without polymers were also prepared and characterized. All vesicles were similar: they were spherical, multilamellar and able to incorporate good amount of rifampicin (EE% ∼ 55%). The addition of the polymers to the formulations allowed an increase of mean diameter. All the glycerosomes, in particular HY-glycerosomes, were able to deliver the drug to the furthest stages of the Next Generation Impactor and the aptitude of the vesicles to be nebulized was always higher than that of drug dispersion. Rifampicin nanoincorporation in vesicles reduced the in vitro drug toxicity on A549 cells, as well as increased its efficacy against Staphylococcus aureus. Finally, the in vivo biodistribution and accumulation, evaluated after intra-tracheal administration to rats, confirmed the improvement of rifampicin accumulation in lungs.

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