Pyrazinoic acid-poly(malic acid) biodegradable nanoconjugate for efficient intracellular delivery.

• Autor(a) principal: Carneiro, Simone Pinto
• Data de Publicação: 2019
• Outros Autores: Moine, Laurence, Tessier, Barbara, Valérie, Nicolas, Santos, Orlando David Henrique dos, Fattal, Elias
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFOP
• Texto Completo: http://www.repositorio.ufop.br/handle/123456789/12246; https://doi.org/10.33218/prnano2(3).190523.1
• topic: Tuberculosis

Tuberculosis is an infectious disease affecting mostly lungs, that is still considered a health global problem as it causes millions of deaths worldwide. Current treatment is effective but associated with severe adverse effects due to the high doses of each anti-tuberculosis drug daily administrated by oral therapy. For the first time, a pyrazinoic acid (PA) biodegradable nanoconjugate was synthesized and developed for pulmonary administration in an attempt to reduce the administered doses by achieving a high drug payload and controlled release at the target site. The conjugate was synthesized by coupling pyrazinoic acid on carboxylic groups of poly(malic acid), which is a biodegradable and biocompatible polymer, and posteriorly self-assembled into nanoconjugates. Characterization confirmed the formation of nanometric, spherical and negatively charged pyrazinoic acid nanoconjugate (NC-PA). NC-PA was stable for 60 days at 4 and 37°C and able to deliver PA in a sustained release manner over time. On macrophages, they exhibited no cell toxicity for a wide range of concentrations (from 1 to 100 µg/mL), demonstrating the safety of NC-PA. In addition, the nanoconjugate was efficiently taken up by RAW 264.7 cells over 6 hours reaching a maximum value after 3 hours of incubation. In conclusion, innovative nanoconjugates are a promising alternative to deliver drugs directly to the lungs and contributing to improving tuberculosis therapy.