NOVEL RESPIRABLE RIFAMPICIN-CURCUMIN LOADED NANOPARTICLES AGAINST Mycobacterium tuberculosis INFECTION

PALMAS L.; DONNOLI LUCIA; MORELLI PAULA; BERNABEU E.; MORETTON M.; MARTINENA CAMILA; MARTÍN CANDELA; RIEDEL J.; AMIANO NICOLAS; CHIAPETTA D.; ALARCON L.; RIEMER CAROLINA; PELLEGRINI JOAQUIN; GARCIA VERONICA; TATEOSIAN NANCY L

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2020

SAI, SAIC, SAFIS

Rifampicin (RIF) is one of the most powerful and effective first line drug employedin the treatment of Mycobacterium tuberculosis (Mtb) infection. With the worldwideemergence of highly drug-resistant tuberculosis (TB), novel agents that have directantimycobacterial effects or that enhance host immunity are urgently needed. Itwas described the immunomodulatory anti-TB effects of Curcumin (CUR), a potentanti-oxidant and apoptosis inducer compound. We develop novel RIF-CURnanoparticles (RIF-CUR NP) with improved drug aqueous solubility and stability forinhalator administration. Then, we analyzed by confocal microscopy the in vitrouptake of CUR-NP (20 µg/ml) in human macrophages (derived from PBMCs) atdifferent time points (1h, 18h, 24h and 48h). We found a higher drug cellularuptake levels (intensity/ area) for Mtb antigen-stimulated cells (0.25±0.04) thanunstimulated control (0.07±0.02) over 18 hours (ANOVA test, p<0.05). Finally, invitro studies showed the higher microbicidal effect (CFU counts) of the RIF-CURNP (1µg/ml-1.25µg/ml) versus RIF-NP (1µg/ml) in THP-1 cells infected withMtbH37Rv at 48hours and 4 days (ANOVA test, p<0.05). In summary, the RIF-CUR nanocarrier provides a new simple nanotechnological alternative for itspotential application in respirable TB therapy.