title: Inhalable polymer-glycerosomes as safe and effective carriers for rifampicin delivery to the lungs.
abstract: Rifampicin loaded glycerosomes, vesicles composed of phospholipids, glycerol and water, were combined with trimethyl chitosan chloride (TMC) to prepare TMC-glycerosomes or, alternatively, with sodium hyaluronate (HY) to obtain HY-glycerosomes. These new hybrid nanovesicles were tested as carriers for pulmonary delivery of rifampicin. Glycerosomes without polymers were also prepared and characterized. All vesicles were similar: they were spherical, multilamellar and able to incorporate good amount of rifampicin (EE%∼55%). The addition of the polymers to the formulations allowed an increase of mean diameter. All the glycerosomes, in particular HY-glycerosomes, were able to deliver the drug to the furthest stages of the Next Generation Impactor and the aptitude of the vesicles to be nebulized was always higher than that of drug dispersion. Rifampicin nanoincorporation in vesicles reduced the in vitro drug toxicity on A549 cells, as well as increased its efficacy against Staphylococcus aureus. Finally, the in vivo biodistribution and accumulation, evaluated after intra-tracheal administration to rats, confirmed the improvement of rifampicin accumulation in lungs.
authors.affiliation: Dept. Farmacia y Tecnologia Farmaceutica, University of Valencia, 46100-Burjassot, Valencia, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Melis
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy. Electronic address: mlmanca@unica.it.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.affiliation: Dept. Scienze Biomediche, University of Cagliari, Cagliari, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bullita
authors.affiliation: Dept. Scienze Biomediche, University of Cagliari, Cagliari, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tamburini
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Castangia
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cardia
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Valenti
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.affiliation: Dept. Farmacia y Tecnologia Farmaceutica, University of Valencia, 46100-Burjassot, Valencia, Spain.
authors.forename: José E
authors.initials: JE
authors.lastname: Peris
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
mesh_terms: D000072283:A549 Cells; D000280:Administration, Inhalation; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013211:Staphylococcus aureus / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D008081:Liposomes; D011108:Polymers; D005990:Glycerol; D012293:Rifampin
keywords: A549 cells; Glycerol; In vivo distribution; Phospholipid vesicles; Pulmonary nebulization; Sodium hyaluronate; Trimethyl chitosan chloride