(536b) Anti-Biofilm Efficacy of Biodegradable Nanoparticles to Delivery Novel Antimicrobial Agents

Infections from microbial biofilm formations remain a big threaten to patients, resulting in prolonged pain and increased medical expenses. For example, patient with pulmonary diseases, such as tuberculosis and cystic fibrosis, experience polymicrobial airway colonization with pathogens including Staphylococcus aureus, Burkholderia cepacia and predominantly, Pseudomonas aeruginosa (PA), which cause intense inflammation in the lungs. A progressive decline in lung function usually occurs, which can lead to respiratory failure and death.  Present treatment for biofilm infection in patients consists of frequent high-dose administration of intravenous antibiotics. Even with this type of aggressive therapy, complete eradication of the bacteria is difficult, due to the ability of the organisms to form biofilms. Persistence of bacteria has lead to the rise of resistant bacterial strains with enhanced tolerance to current antibiotics. Consequently, novel strategies for the efficient delivery of new anti-biofilm therapies are needed. The goal of this proposed research is to develop polymeric nano-particles (NPs) that will deliver novel non-antibiotic anti-biofilm therapies. In this study, we developed a mixture drug delivery system containing two biodegradable nanoparticles (NPs) encapsulated with two complementary therapies; (a) an EPS polysaccharide dispersant and (b) a Ga-siderophore based antibacterial agent to enhance drug transport and uptake for the treatment of biofilm infection diseases.

In this study, we have developed a combination of PLGA and Alginate NPs to release effective therapeutic amounts of Ga-complexes and DNase (or DispersinT^M). Ga-complexes have had shown significant bacterial killing effects on both gram-positive (Staphylococcus epidermidis, SE) and gram negative (Pseudomonas aeruginosa, PA) bacteria at a relative low minimal inhibitory concentration. The DNase (or DispersinT^M) enzymes can effectively remove EPS matrix in specific SE and PA biofilms. Enzyme-based therapies in combination with antimicrobial PPIX-Ga produced Synergic effects of reducing biofilm formation. PPIX-complexes and Dispersin^TM were promising non-antibiotic therapeutic drugs that could be released from the biodegradable NPs, thus enhancing the treatment effects of biofilm infection related diseases.