Co-encapsulation of Totarol and Adjuvant Silver in Block Co-polymer Nanoparticles

Abstract

Bacterial resistance to antibiotics is a significant problem in the world today contribution 20 billion dollars to healthcare costs, adds 8 million days of hospitalization, and causing 23,000 deaths annually. The pipeline for new antibiotics has been shrinking and a new broad spectrum antibiotic has not emerged within the last 40 years. Antibiotic adjuvants are compounds that potentiate the activity of antibiotics, either sensitizing new targets to the antibiotic or re-sensitizing formerly viable targets. Silver potentiates the activity of a number of antibiotics against both gram-positive and gram-negative bacteria. Current antibiotic delivery methods are non-localized, non-targeted, and non-specific. Delivery of antibiotics by nanoparticles helps to overcome these weaknesses. FlashNanoprecipitation (FNP) is an economical and scalable method of producing large quantities of polymeric nanoparticles containing hydrophobic antibiotics. Co-encapsulating antibiotics with adjuvants has the additional benefit of co-delivering a compound that potentiates antibiotic activity. We developed formulations for polymeric nanoparticles containing the antibiotic totarol and adjuvant silver nanoparticles stabilized by oleic acid. We investigated the tunability of particle size, stability, and release rate by varying nanoparticle formulations. Biological assays indicated adjuvant synergistic behavior between silver and totarol against S. aureus, and the effect of nanoparticle formulation on biological activity was investigated. These assays suggest that co-encapsulation of antibiotics and adjuvants in polymeric nanoparticles is a promising technique to mitigate the problem of antibiotic resistance.