title: Synthesis and characterization of the antitubercular phenazine lapazine and development of PLGA and PCL nanoparticles for its entrapment.
abstract: The aim of this work was to develop and characterize nanoparticles as carriers of lapazine, a phenazine derived from β-lapachone; its antimycobacterial activity is described for the first time as a potential treatment for tuberculosis. The lapazine was synthesized, and by using gas chromatography coupled to a flame ionization detector, it was possible to evaluate its purity degree of almost 100%. For better elucidation of the molecular structure, mass spectroscopy and 1H NMR were carried out and compared to the literature values. Lapazine was assayed in vitro against H37Rv Mycobacterium tuberculosis and a rifampicin-resistant strain, with minimum inhibitory concentration values of 3.00 and 1.56 μg mL(-1), respectively. The nanoparticles showed a polydispersity index of 0.16,mean diameter of 188.5 ± 1.7 mm, zeta potential of -15.03 mV, and drug loading of 54.71 mg g(-1) for poly-ε-caprolactone (PCL) nanoparticles and a polydispersity index of 0.318,mean diameter of 197.4 ± 2.7 mm, zeta potential of -13.43 mV and drug loading of 137.07 mg g(-1) for poly(DL-lactide-co-glycolide) (PLGA) nanoparticles. These results indicate that both polymeric formulations have good characteristics as potential lapazine carriers in the treatment of tuberculosis.
authors.affiliation: Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Produtos Naturais e Alimentos, Rio de Janeiro, Brazil.
authors.forename: Narjara
authors.initials: N
authors.lastname: Silveira
authors.affiliation: Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Produtos Naturais e Alimentos, Rio de Janeiro, Brazil.
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Longuinho
authors.affiliation: Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Produtos Naturais e Alimentos, Rio de Janeiro, Brazil.
authors.forename: Suzana G
authors.initials: SG
authors.lastname: Leitão
authors.affiliation: Núcleo de Ciências Químicas, Instituto de Educação, Ciência e Tecnologia do Rio de Janeiro, Campus Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Raphael S F
authors.initials: RS
authors.lastname: Silva
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, Laboratório de Bacteriologia e Bioensaios em Micobactérias, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Lourenço
authors.affiliation: Universidade Federal do Rio Grande, FURG, Laboratório de Micobactérias, Rio Grande, RS, Brazil.
authors.forename: Pedro E A
authors.initials: PE
authors.lastname: Silva
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Pesquisa de Produtos Naturais, Rio de Janeiro, Brazil.
authors.forename: Maria do Carmo F R
authors.initials: Mdo C
authors.lastname: Pinto
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biológicas, RJ, Brazil.
authors.forename: Leida G
authors.initials: LG
authors.lastname: Abraçado
authors.affiliation: Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Produtos Naturais e Alimentos, Rio de Janeiro, Brazil. Electronic address: pfinotelli@gmail.com.
authors.forename: Priscilla V
authors.initials: PV
authors.lastname: Finotelli
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065546:Drug Liberation; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D000995:Antitubercular Agents; D010619:Phenazines; D011091:Polyesters; C000609768:lapazine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Drug loading; Drug release; Lapazine; PCL nanoparticles; PLGA nanoparticles; Tuberculosis