title: Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.
abstract: Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: Rafaela S
authors.initials: RS
authors.lastname: Ferraz-Carvalho
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Pereira
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brasil.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Linhares
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: Mariane Cb
authors.initials: MC
authors.lastname: Lira-Nogueira
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: Isabella Mf
authors.initials: IM
authors.lastname: Cavalcanti
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: Nereide S
authors.initials: NS
authors.lastname: Santos-Magalhães
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brasil.
authors.forename: Lílian Ml
authors.initials: LM
authors.lastname: Montenegro
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002214:Capsules; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008081:Liposomes; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D001572:Benzofurans; D002214:Capsules; D008081:Liposomes; C073339:usnic acid; D007538:Isoniazid; D012293:Rifampin