Tailored Nanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas aeruginosa: A Comparative Study
Abstract
Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time, and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa. We prepared and compared poly(lactic acid)-grafted-poly(ethylene glycol) nanoparticles, as well as anionic and cationic liposomes for their size, charge, and encapsulation efficiency. Cationic liposomes were unable to encapsulate any drug and were subsequently considered as a control formulation. Regarding the efficiency of the nanocarrier, anionic liposomes exhibited a prolonged release over 72 h and preserved the antibacterial activity of levofloxacin against five strains of P. aeruginosa, whereas polymeric nanoparticles quickly released their entire payload and increased the minimum inhibitory concentration of levofloxacin. Thus, only anionic liposomes were considered for further preclinical development. Anionic liposomes exhibited a suitable colloidal stability in Turbiscan analysis and crossed a layer of artificial mucus in under 1 h in a Transwell setup. Despite their negative surface charge, liposomes still interacted with the P. aeruginosa membrane in a dose-response manner, as demonstrated…
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