Pyrazinoic acid-Poly(malic acid) biodegradable nanoconjugate for efficient intracellular delivery
Pyrazinoic acid-Poly(malic acid) biodegradable nanoconjugate for efficient intracellular delivery
Résumé
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.
Domaines
Biomatériaux
Origine : Fichiers produits par l'(les) auteur(s)
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