title: Fabrication of polyelectrolyte multilayered vesicles as inhalable dry powder for lung administration of rifampicin.
abstract: A polyelectrolyte complex based on chitosan and carrageenan was used to coat rifampicin-loaded vesicles and obtain a dry powder for inhalation by spray-drying. The polymer complexation on vesicle surface stabilized them and improved their adhesion on airways and epithelia cells. Uncoated liposomes were small in size, negatively charged and able to incorporate large amounts of rifampicin (70%). Coated vesicles were still able to load adequate amounts of drug (∼70%) but the coating process produced larger particles (1 μm) that were positively charged and with a spherical shape. Aerosol performances, evaluated using the next-generation impactor, showed that coated vesicles reached the 50% of fine particle fraction and the smallest mass median aerodynamic diameter (2 μm). Rifampicin-loaded uncoated and coated vesicles slowly reduced the A549 cell viability over a 48-h incubation time. Moreover, in vitro coated formulations had a strong ability to be easily internalized and to greatly prolong the residence time of their components in A549 cells compared to uncoated liposomes that were rapidly internalized and just as quickly removed.
authors.affiliation: Department of Environmental and Life Science, University of Cagliari, Via Ospedale 72, Cagliari 09124, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.affiliation: Department of Environmental and Life Science, University of Cagliari, Via Ospedale 72, Cagliari 09124, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Valenti
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Burjassot, Valencia 46100, Spain.
authors.forename: Octavio Diez
authors.initials: OD
authors.lastname: Sales
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Burjassot, Valencia 46100, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Nacher
authors.affiliation: Department of Environmental and Life Science, University of Cagliari, Via Ospedale 72, Cagliari 09124, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.affiliation: Department of Environmental and Life Science, University of Cagliari, Via Ospedale 72, Cagliari 09124, Italy. Electronic address: manconi@unica.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
mesh_terms: D000280:Administration, Inhalation; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D002351:Carrageenan / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D008081:Liposomes; D010316:Particle Size; D012293:Rifampin / Q000008:administration & dosage*; D014961:X-Ray Diffraction
chemical_list: D000904:Antibiotics, Antitubercular; D008081:Liposomes; D002351:Carrageenan; D048271:Chitosan; D012293:Rifampin
keywords: Carrageenan; Chitosan; Coated liposomes; Next-generation impactor; Pulmonary delivery; Rifampicin