Antibody Conjugated Nanocarriers for Targeted Antibiotic Delivery: Application in the Treatment of Bacterial Biofilm Infections

Abstract

Conventional antibiotic treatment is in most cases insufficient to eradicate biofilm-related infections, resulting in high risk of treatment failure and recurrent infections. Recent studies have shown that novel methods of antibiotic delivery can improve clinical outcomes and reduce the emergence of antibiotic resistance. The objectives of this work were to develop and evaluate a targeting nanocarrier system that enables effective delivery of antimicrobial drugs to Staphylococcus aureus, a commonly virulent human pathogen. For this purpose, we first prepared a formulation of polymeric nanoparticles suitable for encapsulation and sustained release of antibiotics. A specific antibody against S. aureus was used as targeting ligand and was covalently immobilized onto the surface of nanoparticulate materials. It was demonstrated that the targeting nanoparticles preferentially bound S. aureus cells and presented an elevated accumulation in S. aureus biofilm. Compared to free form antibiotic, the antibiotic-loaded targeting nanoparticles significantly enhanced in vitro bactericidal activity against S. aureus both in planktonic and biofilm forms. Using a mouse infection model, we observed improved therapeutic efficacy of these antibiotic-loaded nanoparticles after a single intravenous administration. Taken together, our studies show that the targeting nanoparticulate system could be a promising strategy to enhance the biodistribution of antibiotics and thereby improve their efficacy.