Formulation et évaluation de nanovecteurs polymères porteurs d'anticorps pour une délivrance ciblée d'antibiotiques
Abstract
Conventional antibiotic treatment of chronic infections becomes currently challenging due to rising rates of antibiotic resistance. Recent studies have shown that changes in method of antimicrobial drug delivery, especially the advantages of targeted nanomedicine can improve antibiotherapy efficacy, reduce the emergence of antibiotic resistance and increase the lifespan of new antibiotics. The objective of this work is to investigate the antibacterial efficacy of antibiotic-loaded polymeric nanoparticles and their selective targeting to Staphylococcus aureus, a common and virulent human pathogen. For this purpose, we have developed a formulation of poly(lactic-co-glycolic acid) (PLGA) based nanoparticles for encapsulating different types of antibiotics (ciprofloxacin, levofloxacin, rifampicin). A specific antibody of S. aureus was then covalently immobilized onto nanoparticles for targeted antibiotic delivery. The elaboration of nanoparticles was optimized in terms of particle size, antibody conjugation efficiency and drug loading. In vitro, the targeted nanoparticles bound specifically to the surface of S. aureus, penetrated and accumulated selectively in S. aureus biofilm. Compared to the untargeted antibiotic-loaded nanoparticles or free antibiotics, the targeted antibiotic-loaded nanoparticles showed significant improvement in bactericidal activity against S. aureus. In the mouse biofilm model, the antibiotic-loaded nanoparticles had a successful targeting to S.…
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