In vitro and in vivo antimicrobial activity of sodium colistimethate and amikacin-loaded nanostructured lipid carriers (NLC)

Sodium colistimethate (SCM) and amikacin (AMK) are among the few antibiotics effective against resistant P. aeruginosa, K. pneumoniae and A. baumannii; however, their toxicity severely limits their use. Enclosing antibiotics into nanostructured lipid carriers (NLC) might decrease drug toxicity and improve antibiotic disposition. In this work, SCM or AMK was loaded into different NLC formulations, through high pressure homogenization, and their in vitro and in vivo effectiveness was analyzed. The encapsulation process did not reduce drug effectiveness since in vitro SCM-NLC and AMK-NLC drug activity was equal to that of the free drugs. As cryoprotectant, trehalose showed better properties than dextran. Instead, positive chitosan coating was discarded due to its limited cost-efficiency. Finally, the in vivo study in acute pneumonia model revealed that intraperitoneal administration was superior to the intramuscular route and confirmed that (−) SCM-NLC with trehalose, was the most suitable formulation against an extensively drug-resistant A. baumannii strain. In this work, colistin or amikacin was loaded into different NLC formulations and their in vitro and in vivo effectiveness was analyzed. Negatively charged Colistin-NLC, with trehalose as cryoprotectant, were selected for their better in vitro efficacy in several bacteria strains, especially in A. baumannii. Finally, the in vivo efficacy study revealed that Colistin-NLC could represent a promising option to fight against resistant pulmonary infections due to A. baumannii and successfully tackle the alarming AMR problem. [Display omitted]