In Vivo Efficacy of a Nanoconjugated Glycopeptide Antibiotic in Silkworm Larvae Infected by Staphylococcus aureus.

Simple Summary: Novel therapeutic treatments are urgently needed to tackle the increasing number of bacterial pathogens becoming resistant to the currently available antibiotics. One promising perspective to improve antibiotic efficacy is their conjugation to nanoparticles. Nanoconjugated antibiotics can be directed to infection sites, facilitating tissue penetration and reducing side effects. A possible bottleneck in the pipeline to develop nanoconjugated antibiotics is their in vivo testing in animal models. Since the use of mammals—i.e., the gold standard for animal testing—is limited due to economic and ethical issues, we propose a non-mammalian infection model based on the silkworm. Herein, this model is used to evaluate the efficacy of teicoplanin conjugated to iron oxide nanoparticles. Teicoplanin is a life-saving glycopeptide antibiotic for the treatment of severe infections by Gram-positive bacterial pathogens, and iron oxide nanoparticles represent a promising tool for delivering this glycopeptide antibiotic to the infection site, increasing local efficacy and reducing off-target effects. To contrast the rapid spread of antibiotic resistance in bacteria, new alternative therapeutic options are urgently needed. The use of nanoparticles as carriers for clinically relevant antibiotics represents a promising solution to potentiate their efficacy. In this study, we used Bombyx mori larvae for the first time as an animal model for testing a nanoconjugated glycopeptide antibiotic (teicoplanin) against Staphylococcus aureus infection. B. mori larvae might thus replace the use of mammalian models for preclinical tests, in agreement with the European Parliament Directive 2010/63/EU. The curative effect of teicoplanin (a last resort antibiotic against Gram-positive bacterial pathogens) conjugated to iron oxide nanoparticles was assessed by monitoring the survival rate of the larvae and some immunological markers (i.e., hemocyte viability, phenoloxidase system activation, and lysozyme activity). Human physiological conditions of infection were reproduced by performing the experiments at 37 °C. In this condition, nanoconjugated teicoplanin cured the bacterial infection at the same antibiotic concentration of the free counterpart, blocking the insect immune response without causing mortality of silkworm larvae. These results demonstrate the value and robustness of the silkworm as an infection model for testing the in vivo efficacy of nanoconjugated antimicrobial molecules. [ABSTRACT FROM AUTHOR]