Nanoparticulate β-Cyclodextrin with Gallium Tetraphenylporphyrin Demonstrates in Vitro and in Vivo Antimicrobial Efficacy against Mycobacteroides abscessus and Mycobacterium avium

• DOI: 10.1021/acsinfecdis.0c00896
• Publication Date: 2021-07-27T18:43:33Z
• Authors: Seoung-Ryoung Choi; Geoffrey A. Talmon; Bradley E. Britigan; Prabagaran Naraya...
• Keywords: Hemin; Lactoferrin

The emergence of drug-resistant pathogens causes the greatest challenge for drug development research. Recently, gallium(III)-based compounds have received great attention as novel antimicrobial agents against pathogens. Here, we synthesized a new β-cyclodextrin Ga nanoparticle (CDGaTP) using tetraphenylporphyrin (GaTP, hemin analogue) and β-cyclodextrin. newly was nontoxic efficient at single dose, showing sustained release 15 days in vitro. CDGaTP's activity with transferrin or lactoferrin tested, synergism observed nontuberculosis mycobacteria (NTM), Mycobacterium avium (M. avium), Mycobacteroides abscessus. Human serum albumin (HSA) decreased efficacy both GaTP CDGaTP concentration-dependent manner. NTMs incubated significantly produced reactive oxygen species (ROS), indicating potential inhibition antioxidant enzymes, such catalase. single-dose displayed prolonged intracellular inhibitory an vitro macrophage infection model NTMs. In addition, CDGaTP, not GaTP, effective murine lung M. when delivered via intranasal administration. These results suggest that provides opportunities gallium-porphyrin based antibiotics.