Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.

Rafaela S Ferraz-Carvalho,Lílian Ml Montenegro,Leonardo A Linhares,Marcela A Pereira,Nereide S Santos-Magalhães,Isabella Mf Cavalcanti,Mariane Cb Lira-Nogueira

doi:10.1590/0074-02760150454

Rafaela S Ferraz-Carvalho, Lílian Ml Montenegro + Show 5 more

Open Access

https://doi.org/10.1590/0074-02760150454

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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.

Highlights

Tuberculosis (TB) is a chronic bacterial infection caused by an airborne microorganism known as Mycobacterium tuberculosis (Mtb)
Checkerboard method - The in vitro interactions were evaluated in two multidrug-resistant tuberculosis (MDR-TB) isolates (1619 and 1411) as these isolates presented the minimum inhibitory concentration (MIC) values set for the reference and tested drugs
Conventional liposomes were selected as vehicles for Usnic acid (UA) because they are suitable carriers for antibiotics used in the treatment of intracellular pathogens, such as Mtb (Drulis-Kawa & Dorotkiewicz-Jach 2010)

Summary

Introduction

Tuberculosis (TB) is a chronic bacterial infection caused by an airborne microorganism known as Mycobacterium tuberculosis (Mtb). Nanotechnology has emerged as an efficient tool able to enhance drug efficacy and overcome the resistance of Mycobacterium against well-known antibiotics usually prescribed in clinical practice (Yempala et al 2013). These advantages, associated with the fact that only one anti-TB drug (TMC207) has been approved by the United States Food and Drug Administration in the last four decades, indicate the feasibility of nanosystems, such as liposomes containing antimycobacterial drugs (Ganihigama et al 2015). The aim of our study was to evaluate the effect of UA encapsulation into liposomes (UA-Lipo) and its combinations with RIF or INH, against MDR-TB clinical isolates

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