PT  - JOURNAL ARTICLE
AU  - Joel A. Finbloom
AU  - Preethi Raghavan
AU  - Michael Kwon
AU  - Bhushan N. Kharbikar
AU  - Michelle A. Yu
AU  - Tejal A. Desai
TI  - Co-Delivery of Synergistic Antimicrobials with Polyelectrolyte Nanocomplexes to Treat Bacterial Biofilms and Lung Infections
AID  - 10.1101/2021.11.22.469570
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.11.22.469570
4099  - http://biorxiv.org/content/early/2022/09/15/2021.11.22.469570.short
4100  - http://biorxiv.org/content/early/2022/09/15/2021.11.22.469570.full
AB  - New approaches are needed to treat bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA), which have high rates of antimicrobial resistance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeutics that act synergistically can overcome resistance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a new nanoscale drug carrier for antimicrobial co-delivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs leading to complete biofilm eradication. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic co-delivery to overcome antimicrobial resistant bacterial infections.Competing Interest StatementT.A.D. is a scientific founder of Oculinea, Encellin, VasaRx, and Biothelium.