Drug-loaded liposomes for macrophage targeting in Mycobacterium tuberculosis: development, characterization and macrophage infection study.

Abstract

This study investigates drug-loaded liposomes targeting macrophages as a promising strategy to enhance Tuberculosis (TB) treatment. The focus is on optimizing liposomal formulations for encapsulating OX-23, a previously identified anti-mycobacterial agent with a minimum inhibitory concentration (MIC) of 1.56 µg/ml, and assessing their efficacy in macrophage infection models. Liposomal formulations were characterized for particle size, polydispersity index (PDI), and zeta potential using dynamic light scattering (DLS), with morphology analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Macrophage infection assays, including those with the THP-1 macrophage cell line, were performed to evaluate the targeting efficiency and therapeutic potential of the formulations. Results showed that OX-23 could be successfully encapsulated in liposomes with various charges, achieving high encapsulation efficiency, optimal particle size, and acceptable PDI values. In-vitro studies with the THP-1 cell line demonstrated sustained release of the drug from the liposomes, with morphological analysis confirming that the liposomes were spherical and non-aggregated. The formulations exhibited significant penetration into infected macrophages and effectively inhibited the growth of intracellular Mycobacterium tuberculosis at the tested concentrations. These findings support the potential of liposomal OX-23 in targeting both extracellular and intracellular M. tuberculosis, offering a promising approach to TB treatment.