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Rifampicin-Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation.

ABSTRACT: Treatment of pulmonary infections caused by Mycobacterium abscessus are extremely difficult to treat, as this species is naturally resistant to many common antibiotics. Liposomes are vesicular nanocarriers suitable for hydrophilic and lipophilic drug loading, able to deliver drugs to the target site, and successfully used in different pharmaceutical applications. Moreover, liposomes are biocompatible, biodegradable and nontoxic vesicles and nebulized liposomes are efficient in targeting antibacterial agents to macrophages. The present aim was to formulate rifampicin-loaded liposomes (RIF-Lipo) for lung delivery, in order to increase the local concentration of the antibiotic. Unilamellar liposomal vesicles composed of anionic DPPG mixed with HSPC for rifampicin delivery were designed, prepared, and characterized. Samples were prepared by using the thin-film hydration method. RIF-Lipo and unloaded liposomes were characterized in terms of size, ζ-potential, bilayer features, stability and in different biological media. Rifampicin's entrapment efficiency and release were also evaluated. Finally, biological activity of RIF-loaded liposomes in Mycobacterium abscessus-infected macrophages was investigated. The results show that RIF-lipo induce a significantly better reduction of intracellular Mycobacterium abscessus viability than the treatment with free drug. Liposome formulation of rifampicin may represent a valuable strategy to enhance the biological activity of the drug against intracellular mycobacteria.

SUBMITTER: Rinaldi F

PROVIDER: S-EPMC8309174 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Mucoadhesive Rifampicin-Liposomes for the Treatment of Pulmonary Infection by Mycobacterium abscessus: Chitosan or ε-Poly-L-Lysine Decoration

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Dissecting the antibacterial activity of Oxadiazolone-core derivatives against Mycobacterium abscessus

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| S-EPMC9767372 | biostudies-literature

In Vitro and Intracellular Activity of Imipenem Combined with Rifabutin and Avibactam against Mycobacterium abscessus.

Project description:Repurposing drugs may be useful as an add-on in the treatment of Mycobacterium abscessus pulmonary infections, which are particularly difficult to cure. M. abscessus naturally produces a ?-lactamase, BlaMAb, which is inhibited by avibactam. The recommended regimens include imipenem, which is hydrolyzed by BlaMAb and used without any ?-lactamase inhibitor. Here, we determine whether the addition of rifabutin improves the activity of imipenem alone or in combination with avibactam against M. abscessus CIP104536. Rifabutin at 16 ?g/ml was only bacteriostatic (MIC of 4 ?g/ml) and was moderately synergistic in combination with imipenem (fractional inhibitory concentration [FIC] index of 0.38). Addition of rifabutin (16 ?g/ml) moderately increased killing by a low (8 ?g/ml) but not by a high (32 ?g/ml) concentration of imipenem. Addition of avibactam (4 ?g/ml) did not further increase killing by the former combination. In infected macrophages, rifabutin (16 ?g/ml) increased the activity of imipenem at 8 and 32 ?g/ml, achieving 3- and 100-fold reductions in the numbers of intracellular bacteria, respectively. Avibactam (16 ?g/ml) improved killing by imipenem at 8 ?g/ml. A 5-fold killing was obtained for a triple combination comprising avibactam (16 ?g/ml) and therapeutically achievable doses of imipenem (8 ?g/ml) and rifabutin (1 ?g/ml). These results indicate that the imipenem-rifabutin combination should be further considered for the treatment of M. abscessus pulmonary infections in cystic fibrosis patients and that addition of a ?-lactamase inhibitor might improve its efficacy. Mechanistically, the impact of BlaMAb inhibition by avibactam on antibiotic activity was assessed by comparing CIP104536 and a ?-lactamase-deficient derivative.

| S-EPMC6105861 | biostudies-other

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