Promoting the Efficacy of Deferiprone-Gallium-Protoporphyrin (IX) against <i>Mycobacterium abscessus</i> Intracellular Infection with Lipid Liquid Crystalline Nanoparticles

Nontuberculous mycobacteria (NTM) are among the recalcitrant bacterial strains that cause difficult-to-treat infections for patients with chronic underlying pulmonary conditions. The bacteria's intrinsic resistance to various antibiotics and their ability to infect macrophages enable them to overcome both the host immune response and standard antibiotics. Unconventional approaches to treating NTM-mediated infections are required. Using the heme mimic agent gallium protoporphyrin (GaPP) and the iron chelator deferiprone (DEF) in combination has been proven as an effective strategy against different bacteria including NTM in vitro. To enable more effective delivery and promote the activity of DEF/GaPP against intracellular NTM infections, both compounds are loaded in lipid liquid crystalline nanoparticles (LCNP). GaPP and DEF are sufficiently entrapped in LCNP with entrapment efficiency of 98% ± 2.1 and 39.4% ± 4.2, respectively. DEF/GaPP LCNP has an average diameter of 171 nm ± 10.2 with a uniform size distribution. DEF/GaPP LCNP reduces the viability of <i>Mycobacterium abscessus</i> intracellular infection by 3.34 log₁₀ in comparison to the control group and is significantly more efficacious than nonformulated DEF/GaPP. Furthermore, DEF/GaPP LCNP is nontoxic to human bronchial epithelial cells in vitro. These findings are envisaged to pave the way for future progress in eradicating NTM-mediated infections.