Liposomes are tiny lipid-based vesicles composed of one or more lipid bilayers, which facilitate the encapsulation of hydrophilic, lipophilic, and amphiphilic biological active agents. The description of the physicochemical properties, formulation methods, characteristics, mechanisms of action, and large-scale manufacturing of liposomes as delivery systems are deeply discussed. The benefits, toxicity, and limitations of the use of liposomes in pharmacotherapeutics including in diagnostics, brain targeting, eye and cancer diseases, and in infections are provided. The experimental approaches that may reduce, or even bypass, the use of liposomal drug drawbacks is described. The application of liposomes in the treatment of numerous diseases is discussed.

The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4–32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.

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L'objectif de notre recherche était d'étudier les effets du Phénylalanine-arginine β-naphthylamide (PABN), seul ou en association avec des aminoglycosides et des macrolides sur des souches cliniques de P. aeruginosa isolées de patients atteints de Fibrose kystique (FK). Pour cela, nous avons comparé les concentrations minimales inhibitrices (CMI) et bactéricides (CMB) obtenues en milieu liquide (bouillon de Mueller-Hinton) du PABN, seul ou en association avec des antibiotiques. Même si PABN est un inhibiteur de la pompe à efflux hautement efficace in-vitro, son niveau élevé d'accumulation dans les organes, en particulier les reins, peut-être toxique (Watkins et collab., 2003, p. 4242). Étant donné que les aminoglycosides sont des substrats de pompes à efflux, l'inhibition de l'efflux devrait augmenter la puissance de ces médicaments contre P. aeruginosa. Nous avons constaté que PABN a augmenté l'activité des aminoglycosides et macrolides contre P. aeruginosa. Cependant, il n'a eu aucun effet sur la souche K2733, qui ne comportait aucune des quatre principales pompes retrouvées chez P. aeruginosa (MexABOprM, MexCD-OprJ, MexEF-OprN et MexXY-OprM). En outre, les bactéries traitées avec le PABN ont été plus sensibles à l'érythromycine, un antibiotique auquel P. aeruginosa est intrinsèquement résistante (Morita, Tomida et Kawamura, 2013).

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