Synthesis and characterization of the antitubercular phenazine lapazine and development of PLGA and PCL nanoparticles for its entrapment

• Published in: Materials Science & Engineering C 2016-01, Vol.58, p.458-466
• Main Authors: Silveira, Narjara, Longuinho, Mariana M., Leitão, Suzana G., Silva, Raphael S.F., Lourenço, Maria C., Silva, Pedro E.A., Pinto, Maria do Carmo F.R., Abraçado, Leida G., Finotelli, Priscilla V.
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Drug Liberation; Drug loading; Drug release; Kinetics; Lactic Acid - chemistry; Lapazine; Microbial Sensitivity Tests; Mycobacterium tuberculosis - drug effects; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Particle Size; PCL nanoparticles; Phenazines - chemical synthesis; Phenazines - chemistry; Phenazines - pharmacology; PLGA nanoparticles; Polyesters - chemistry; Polyglycolic Acid - chemistry; Static Electricity; Tuberculosis; X-Ray Diffraction
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2015.08.062

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 1.56μgmL−1, respectively. The nanoparticles showed a polydispersity index of 0.16, mean diameter of 188.5±1.7mm, zeta potential of −15.03mV, and drug loading of 54.71mgg−1 for poly-ε-caprolactone (PCL) nanoparticles and a polydispersity index of 0.318, mean diameter of 197.4±2.7mm, zeta potential of −13.43mV and drug loading of 137.07mgg−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. [Display omitted] •Lapazine has activity against M. tuberculosis, but its lipophilicity restricts in vivo toxicity tests.•Two polymeric nanoparticle systems are proposed for lapazine entrapment.•Polymeric nanoparticles were characterized according to their physical, physical-chemistry properties and release profile.