Evaluation of Antibiotic Release from Polymeric Prodrugs

Abstract

Melioidosis is a bacterial lung infection caused by a pathogen capable of invading alveolar macrophages, where it gains protection from the immune system and antibiotic treatment. These complications necessitate an extensive 2-phase antibiotic treatment regimen that is often cost prohibitive to peoples in many endemic regions. Furthermore, there are currently no FDA approved methods to specifically target the intracellular bacteria populations. To meet this unmet medical need to treat intracellular bacterial infections, we have designed synthetic polymeric prodrugs with cleavable linkers bearing an antibiotic drug. Previously, in vitro experiments using percent drug release to characterize the release kinetics of the prodrugs have been performed. However, acid and base hydrolysis have been used to define complete release of drug from the polymer. The use of two different methods to define percent release prevents certain experiments from being directly compared. Therefore, the overall aim of my research was to validate these methods of quantification to ensure robust methodology and allow for interoperability.