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Promoting the Efficacy of Deferiprone-Gallium-Protoporphyrin (IX) against Mycobacterium abscessus Intracellular
Sholeh Feizi1,2, Muhammed Awad1,2, Mahnaz Ramezanpour1,2
1Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia.
Abstract:
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 Mycobacterium abscessus 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.
Insights
New lipid nanoparticles effectively deliver gallium protoporphyrin (GaPP) and deferiprone (DEF) to combat difficult nontuberculous mycobacteria (NTM) infections. This novel formulation shows significant efficacy against intracellular NTM and is non-toxic to human cells.
Area of Science:
- Bacteriology
- Nanomedicine
- Drug Delivery
Background:
- Nontuberculous mycobacteria (NTM) cause persistent infections due to antibiotic resistance and intracellular survival.
- Standard antibiotic treatments are often ineffective against NTM, necessitating novel therapeutic strategies.
- Gallium protoporphyrin (GaPP) and deferiprone (DEF) show promise against NTM but require improved delivery methods.
Purpose of the Study:
- To develop and evaluate lipid liquid crystalline nanoparticles (LCNP) for enhanced delivery of GaPP and DEF.
- To assess the efficacy of DEF/GaPP loaded LCNP against intracellular *Mycobacterium abscessus* infections.
- To determine the in vitro toxicity of DEF/GaPP LCNP in human bronchial epithelial cells.
Main Methods:
- GaPP and DEF were encapsulated into LCNP, with entrapment efficiencies measured.
- Particle size and distribution of DEF/GaPP LCNP were analyzed.
- The effect of DEF/GaPP LCNP on intracellular *Mycobacterium abscessus* viability was quantified and compared to non-formulated compounds.
Main Results:
- DEF/GaPP LCNP demonstrated high entrapment efficiency for GaPP (98% ± 2.1) and moderate efficiency for DEF (39.4% ± 4.2).
- The nanoparticles exhibited a uniform size distribution with an average diameter of 171 nm ± 10.2.
- DEF/GaPP LCNP significantly reduced intracellular *Mycobacterium abscessus* viability by 3.34 log10 compared to controls and non-formulated DEF/GaPP, with no observed toxicity to human bronchial epithelial cells.
Conclusions:
- Lipid liquid crystalline nanoparticles provide an effective delivery system for the combination of GaPP and DEF.
- DEF/GaPP LCNP demonstrates superior efficacy against intracellular NTM infections compared to the unformulated drugs.
- This nanodelivery approach offers a promising, non-toxic strategy for treating challenging NTM infections.
