ZnPc-LIPOSOMES SYNTHESIS. ANTIMICROBIAL EFFECTS ON MYCOBACTERIUM MULTIDRUG-RESISTANT TUBERCULOSIS (MDR)

M. MIRETTI; M. A. GONZÁLEZ GRAGLIA; L. JURI; C. COSIANSI; T. TEMPESTI; M. T. BAUMGARTNER

Otro; I Fórum On-line de Tecnologias da Luz na Saúde; 2020

Tuberculosis is one of the most important health problems worldwide. Multidrug resistant (MDR)-tuberculosis is caused by MDR-Mycobacterium tuberculosis (M. tuberculosis) resistant to the first line drugs (rifampin-isoniazid).Photodynamic Antimicrobial chemotherapy (PACT) has reemerged as an alternative against resistant bacteria. In this work, we synthesize liposomes of DPPC and cholesterol as carrier of ZnPc (Figure 1), modifying the methodology previously reported. We use DMSO as cosolvent instead of pyridine. DMSO was incorporated into the pharmaceutical excipients manual and is used in several regulated products for healthcare applications and drug delivery. This change improves formulation and reduces the toxicity of pyridine use.The photodynamic activity of ZnPc-liposomes was tested in two strains of M. tuberculosis, a sensible (ATCC 27294) and MDR-M. tuberculosis. Control liposomes did not cause changes in cellular viability. In all cases, photodynamic activity depended on incubation time and light dose supplied. A reduction of 3 log10 CFU/ml or 99.9 % of susceptible M. tuberculosis photoinactivation was achieved after 2 hours of incubation using 75 or 150 J/cm2 as light doses (Graphic 1). While for MDR-M. tuberculosis was necessary to adjust the incubation time to 4 hours and to combine with a higher light dose to generate a decrease of 3 log10 CFU/ml. Conventional medication has limited efficacy for MDR-M. tuberculosis and the treatment has become much more complicated. Therefore, ZnPc-liposomes could be an alternative to treat MDR-M. tuberculosis.