Development and evaluation of Amikacin-loaded carbopol hydrogel for topical treatment of <i>Mycobacterium marinum</i> skin infections

Mycobacterium marinum is a slow growing Non-Tuberculosis Mycobacteria known to cause skin and subcutaneous tissue infections known as "fish tank granuloma" in humans. Treatment of M. marinum skin infections can last for several months or even years. Intravenous or intramuscular administration of Amikacin, a bactericidal inhibitor, in a multidrug regimen is a good therapeutic option in treating M. marinum infections. No topical hydrogels are currently available to treat M. marinum skin infections. We developed a 2.5% amikacin-loaded carbopol hydrogel containing the permeation enhancers 1% Tween-80 and 1% PEG (AMK-CPTP) for topical application to treat M. marinum skin infections. A molecular docking study of carbopol-Amikacin interaction predicted a stable structure and was confirmed with rheological characterization. The developed gel was found to be non-hemolytic, cytocompatible, and non-irritant. Sustained release of Amikacin from the AMK-CPTP hydrogel was observed, with a release of 60% Amikacin after 48 h. The antibacterial activity and skin permeability of amikacin released from AMK-CPTP were assessed using both in vitro and ex vivo assays. Overall. AMK-CPTP demonstrated anti-microbial activity against M. marinum with a 35% increase in skin permeation on the addition of Tween-80 and PEG. AMK-CPTP could be used to treat M. marinum skin infections.