title: Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis.
abstract: The goal of the work was to evaluate an anti-tubercular strategy based on breathable Solid Lipid Microparticles (SLM) to target alveolar macrophages and to increase the effectiveness of the conventional tuberculosis (TB) therapy. Rifampicin loaded SLM composed of stearic acid and sodium taurocholate were characterized for aerodynamic diameter, surface charge, physical state of the components, drug loading and release as well as drug biological activity on Bacillus subtilis strain. Moreover, SLM cytotoxicity and cell internalization ability were evaluated on murine macrophages J774 cell lines by MTT test, cytofluorimetry and confocal laser microscopy. SLM exhibited aerodynamic diameter proper to be transported up to the alveolar epithelium, negative charged surface able to promote uptake by the macrophages and preserved drug antimicrobial activity. The negligible in vitro release of rifampicin indicated the capacity of the microparticle matrix to entrap the drug preventing its spreading over the lung fluid. In vitro studies on J774 cell lines demonstrated SLM non-cytotoxicity and ability to be taken up by cell cytoplasm. The microparticulate carrier, showing features suitable for the inhaled therapy and for inducing endocytosis by alveolar macrophages, could be considered promising in a perspective of an efficacious TB inhaled therapy by means of a Dry Powder Inhaler device.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Maretti
authors.affiliation: Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, via Campi 287, 41125 Modena, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rossi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Moreno
authors.initials: M
authors.lastname: Bondi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Croce
authors.affiliation: Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Strada Vignolese 905, 41125 Modena, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hanuskova
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Leo
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sacchetti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy. Electronic address: valentina.iannuccelli@unimore.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iannuccelli
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005434:Flow Cytometry; D008055:Lipids / Q000737:chemistry; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D018613:Microscopy, Confocal; D008863:Microspheres; D010316:Particle Size; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D013229:Stearic Acids / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D008055:Lipids; D013229:Stearic Acids; C031183:stearic acid; D013656:Taurocholic Acid; D012293:Rifampin
keywords: Inhaled therapy; Rifampicin; Solid Lipid Microparticles; Tuberculosis