title: Rifampicin-loaded liposomes for the passive targeting to alveolar macrophages: in vitro and in vivo evaluation.
abstract: Mycobacterium avium complex (MAC), the most frequent cause of opportunistic nontuberculous pulmonary infection, is made up of a group of intracellular pathogens that are able to survive and multiply inside lung alveolar macrophages. As nebulized liposomes are reported to be effective to target antibacterial agents to macrophages, in this work we have prepared and characterized re-dispersible freeze-dried rifampicin (RFP)-loaded vesicles by using soy lecithin (SL) and a commercial, enriched mixture of soy phosphatidylcholine (Phospholipon 90, P90) with or without cholesterol. The obtained results showed that RFP could be loaded stably in SL vesicles only when cholesterol was not present in the film preparation, whereas with P90 vesicles, the highest stability was obtained with formulations prepared with P90/cholesterol 7:1 or 4:1 molar ratios. RFP-liposome aerosols were generated using an efficient high-output continuous-flow nebulizer, driven by a compressor. After the experiments, nebulization efficiency (NE%) and nebulization efficiency of the encapsulated drug (NEED%) were evaluated. The results of our study indicated that nebulization properties and viscosity of formulations prepared with the low-transition-temperature phospholipids, SL and P90, are affected by vesicle composition. However, all formulations showed a good stability during nebulization and they were able to retain more than 65% of the incorporated drug. The effect of liposome encapsulation on lung levels of RFP following aerosol inhalation was determined in rats. The in vitro intracellular activity of RFP-loaded liposomes against MAC residing in macrophage-like J774 cells was also evaluated. Results indicated that liposomes are able to inhibit the growth of MAC in infected macrophages and to reach the lower airways in rats.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Cagliari, Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zaru
authors.forename: Chiara
authors.initials: C
authors.lastname: Sinico
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Logu
authors.forename: Carla
authors.initials: C
authors.lastname: Caddeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Lai
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000382:microbiology*; D008297:Male; D051379:Mice; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D012293:Rifampin