Investigating the potential of endolysin loaded chitosan nanoparticles in the treatment of pneumococcal pneumonia

The emergence of antibiotic-resistant strains of Streptococcus pneumoniae poses an increasing threat to mankind globally. Cpl-1, a muramidase is considered as a potential alternative agent to treat drug-resistant pneumococcal strains, but lower half-life limits its therapeutic applications. As an attempt to increase the bioavailability, chitosan-based Cpl-1 delivery system was developed and characterized in an earlier study. In the present study, the chitosan-based Cpl-1 delivery system was evaluated in the treatment of pneumococcal pneumonia. Bacterial load was found to be lowest in lungs, blood, and spleen of animals treated with Cpl-1 loaded chitosan nanoparticles as compared to Cpl-1 and chitosan nanoparticles treated animals. The histopathological analysis also revealed the lowers levels of pneumococcal infection in the lungs of Cpl-1 loaded chitosan nanoparticles treated group. The inflammatory analysis showed a lower level of inflammation in the lungs of encapsulated endolysin treated as compared to free endolysin (Cpl-1) treated animals. Cytokine studies showed a significant decline in the level of pro-inflammatory and anti-inflammatory cytokines was seen in the Cpl-1 loaded nanoparticles treatment group as compared to other groups at 48 and 72 h, supporting the efficacy of treatment. Considering the increased bactericidal activity, the endolysin delivery system represents a potential therapeutic approach for treating drug-resistant cumbersome bacterial infections. The present study is first of its kind where therapeutic potential of the endolysin delivery system was investigated in an animal infection model.