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

Pharmaceutics

Stefano Casciardi¹  Federica De Santis²  Maurizio Fraziano²  Carlotta Marianecci³  Maria Carafa³  Patrizia Nadia Hanieh³  Federica Rinaldi³  Jacopo Forte³  Simona Sennato⁴  Federico Bordi⁴ 

[1] Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, National Institute for Insurance against Accidents at Work (INAIL), Monteporzio Catone, 00144 Rome, Italy;Dipartimento di Biologia, Università di Roma “Tor Vergata” Via della Ricerca Scientifica, 00133 Rome, Italy;Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma-Piazzale Aldo Moro 5, 00185 Rome, Italy;Istituto dei Sistemi Complessi (ISC)-CNR, sede “Sapienza” and Dipartimento di Fisica, Sapienza Università di Roma, 00185 Rome, Italy;

关键词: liposomes;    rifampicin;    Mycobacterium abscessus;    antibiotic resistance;   

DOI  :  10.3390/pharmaceutics13071070

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown