Gallium Protoporphyrin Liquid Crystalline Lipid Nanoparticles: A Third-Generation Photosensitizer against Pseudomonas aeruginosa Biofilms
Muhammed Awad, Timothy J. Barnes, Nicky Thomas, Paul Joyce, Clive A. Prestidge
Abstract
The looming antimicrobial resistance pandemic has encouraged the investigation of antimicrobial photodynamic therapy (aPDT) as a promising technology to combat recalcitrant bacterial infections caused by antibiotic resistant strains. Here, we report on the optimization and effective application of gallium protoporphyrin liquid crystalline lipid nanoparticles (GaPP-LCNP) as a photosensitizer for aPDT against the Gram-negative bacteria P. aeruginosa in both planktonic and biofilm modes of growth. LCNP significantly enhanced the performance of GaPP as photosensitizer by two-fold, which was correlated with higher antibacterial activity, reducing the viability of planktonic P. aeruginosa by 7 log10 using 0.8 µM GaPP-LCNP and a light dose of 17 J.cm−2. Importantly, GaPP-LCNP also reduced the viability of biofilms by 6 log10 at relatively low light dose of 34.2 J.cm−2 using only 3 µM GaPP-LCNP. The high antibiofilm activity of GaPP-LCNP at low GaPP-LCNP dose indicated the high efficiency and safety profile of GaPP-LCNP as a promising platform for photodynamic inactivation of recalcitrant infections.