(524d) 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.