Cooperative Electrostatic Polymer-Antibiotic Nanoplexes

Many pathogenic bacteria can enter phagocytic cells and replicate in them, and these intracellular bacteria are difficult to treat because the recommended antibiotics do not transport into the cells efficiently. Examples include food-borne bacteria such as Salmonella and Listeria as well as more toxic bacteria such as Brucella and the Mycobacteria that lead to tuberculosis. Current treatments utilize aminoglycoside antibiotics that are polar and positively charged and such drugs do not enter the cells in sufficient concentrations to eradicate the intracellular infections. We have developed core-shell polymeric drug delivery vehicles containing gentamicin to potentially overcome this challenge. Pentablock and diblock copolymers comprised of amphiphilic nonionic polyether blocks and anionic poly(sodium acrylate) blocks have been complexed with the cationic aminoglycoside gentamicin. The electrostatic interaction between the anionic polyacrylates and the cationic aminoglycosides form the cores of the nanoplexes, while the amphiphilic nature of the polyethers stabilize their dispersion in physiological media. The amphiphilic nature of the polyethers in the outer shell aid in interaction of the nanoplexes with extra- and intra-cellular components and help to protect the electrostatic core from any physiological media. This thesis investigates the electrostatic cooperativity between the anionic polyacrylates and cationic aminoglycosides and evaluated the release rates of gentamicin as a function of pH.