Nanocarriers for infectious disease control : physical, chemical and biological effects.

Engineered nanomaterials with distinct physicochemical properties have found vast applications in consumer, industrial and pharmaceutical industries. Zerovalent metal nanoparticles such as silver and copper nanoparticles synthesized with specific surface properties can be utilized as non-traditional antimicrobial agents to address the problem of antimicrobial resistance in clinical settings. The characterization of nanoparticles as therapeutic agents or as drug delivery agents is an important component of the drug discovery pipeline. Silver and copper nanoparticles were synthesized via the chemical reduction method with specific surface stabilizing agents. Particle characterization via dynamic light scattering, transmission electron microscopy and spectroscopy confirmed the formation of stable surface stabilized silver and copper nanoparticles with distinct physicochemical characteristics such as unique nanoparticle surface charge. These nanoparticle constructs were tested for antibacterial efficacy against divergent lineages of bacteria species, Escherichia coli, Staphylococcus aureus, and Sphingobacterium multivorum using standardized microbiological assays. These nanoparticles were effective antibacterial agents against the experimental bacteria species, showing a dose dependent antibacterial effect. Antibacterial properties of these nanoparticles were as a result of surface stabilizing agents, surface charge, dose and interactions between bacteria and nanoparticles. Taken alone, bacteria species identity showed minimal effect on antibacterial response to nanoparticle exposure, thus suggesting that the antibacterial mechanism targets highly conserved anatomical and physiological characteristics in the bacterial tree of life. The nanoparticles also demonstrate antibacterial properties at low doses which is suitable for clinical applications. The role of induced generation of reactive oxygen species (ROS) in mammalian and bacteria cells after exposure to the surface stabilized silver and copper nanoparticles was probed. Low toxicity to BEAS-2B human bronchial epithelia cells was observed while nanoparticles induced high levels of ROS in Escherichia coli. Induced ROS showed a positive correlation to bacteria growth inhibition. Metal ion poisoning and nanoparticle effect were shown to drive induced ROS production in varying degrees in both cell types. Further safety and efficacy studies of nanoparticle exposures via in vitro pharmacokinetic models are needed in order to broaden the knowledge perspectives on their use in biomedical applications.