title: Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis.
abstract: This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles' diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175-213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration.
authors.affiliation: IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.affiliation: IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro
authors.affiliation: IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vieira
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Andrade
authors.affiliation: IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000378:metabolism; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010587:Phagocytosis; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000378:metabolism; D017828:Rifabutin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D014465:Ultrasonics
chemical_list: D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D037181:Lectins, C-Type; D008024:Ligands; D008055:Lipids; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017828:Rifabutin; D008358:Mannose
keywords: drug delivery systems; lipid nanoparticles; mannose; nanostructured lipid carriers; rifabutin; tuberculosis