Synthesis of Polyanhydride Particles As An Antibiotic Delivery Platform Against Intracellular Pathogens

Polyanhydride particles elicit unique cellular responses from immune cells by stimulating particle internalization and by directing intracellular trafficking. Through encapsulating antibiotics within the polyanhydride particles we can achieve sustained release of the antimicrobial compounds. The chemistry of the polymer and particle size can be altered to influence the release of the antibiotic and the fate of the particle within target cells can be optimized. Many microbial pathogens protect themselves against immune defenses by residing and replicating within host cells. The sequestered environment within cells not only protects the pathogen from killing by extracellular serum proteins, but also from being exposed to high concentrations of antibiotics. One such pathogen, Brucella abortus, survives and replicates within macrophages. We encapsulated doxycycline in polyanhydride nanoparticles based on sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy)hexane (CPH). Results have demonstrated that encapsulation of antibiotics enables greater antimicrobial activity by improving intracellular delivery and sustaining continual antibiotic release. The overall effective concentration for treatment was significantly lower compared to current standards of treatment with soluble antibiotics.