Isoniazid-loaded multicore magnetic nanoparticles as a facile intervention for combating mycobacterial infection

Abstract

A hybrid first-line tuberculosis antibiotic conjugated programable magnetic nanoplatform for application in precision therapeutics for treating tuberculosis (TB) is described. Here the citrate anion grafted multicore magnetic nanoparticles (MC-IONPs) enable the precise delivery of isoniazid (INH). This approach promotes specificity and synergistically improves the accumulation of isoniazid on the bacterial membrane interface, thus avoiding the need for higher doses for the treatment. Despite the wide use of isoniazid, there has been no optimal dose established for the treatment of TB, which has led to inadequacy in treatment outcomes. Also, the poor drug absorption and lack of proper knowledge of the pharmacokinetics of INH had made the rise of INH-resistant mycobacteria inevitable. The conjugation of INH on MC-IONPs is facilitated by electrostatic interaction. The successful conjugation was analyzed using FTIR (Fourier transform infrared spectroscopy) and zeta/DLS (dynamic light scattering). The nanoconjugate exhibited MIC (minimum inhibitory concentration) at 1.5 μg mL⁻¹ and MBC (minimum bactericidal concentration) at 3.12 μg mL⁻¹. The nanoconjugate was stable for up to 72 h and showed significant inhibition of replicating bacteria in growth kinetics assay. An increase in ROS (reactive oxygen species) formation is noted in cells treated with the INH–MC-IONP nanoconjugate. In the biofilm model, the mycobacterial biofilm is significantly inhibited (96%) at 12.25 μg mL⁻¹ concentration. This nanoconjugate is also effective against persistent mycobacteria. Given these prevailing scenarios the data obtained suggest that this hybrid nanoplatform acts as a promising tool for application in enhancing the effects of INH with lower doses possible.