In vitrouptake and antimycobacterial activity of liposomal usnic acid formulation

Abstract

The cellular uptake and antimycobacterial activity of usnic acid (UA) and usnic acid-loaded liposomes (UA-LIPOs) were assessed on J774 macrophages. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of UA and UA-LIPO against Mycobacterium tuberculosis were determined. Concentrations required to inhibit 50% of cell proliferation (IC₅₀) were 22.5 (±0.60) and 12.5 (±0.26) μg/ml, for UA and UA-LIPO, respectively. The MICs of UA and UA-LIPO were 6.5 and 5.8 μg/mL, respectively. The MBC of UA-LIPO was twice as low (16 μg/mL) as that of UA (32 μg/mL). An improvement in the intracellular uptake of UA-LIPO was found (21.6 × 10⁴ ± 28.3 × 10² c.p.s), in comparison with UA (9.5 × 10⁴ ± 11.4 × 10² c.p.s). In addition, UA-LIPO remains much longer inside macrophages (30 hours). All data obtained from the encapsulation of usnic acid into liposomes as a drug delivery system (DDS) indicate a strong interaction between UA-liposomes and J774 macrophages, thereby facilitating UA penetration into cells. Considering such a process as ruling the Mycobacterium-transfection by magrophages, we could state that associating UA with this DDS leads to an improvement in its antimycobacterial activity.

Keywords::

• Usnic acid
• liposomes
• cellular uptake
• macrophages
• Mycobacterium tuberculosis
• antimycobacterial activity

Acknowledgments

MPSM is grateful for an MSc scholarship from the Brazilian Ministry of Education (CAPES). NSSM and CLS thank the Brazilian Council for Scientific and Technological Development (CNPq) for individual grants (#334946-01 and #141585/2004-08). This research was supported, in part, by the Brazilian Network Research on Nanobiotechnology-Nanobiotec CNPq/MCT.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.