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Polyelectrolyte Nanocomplex Formation Combined with Electrostatic Self-Assembly Enables the Co-Delivery of Synergistic Antimicrobials to Treat Bacterial Biofilms

View ORCID ProfileJoel A. Finbloom, Preethi Raghavan, View ORCID ProfileBhushan N. Kharbikar, View ORCID ProfileMichelle A. Yu, Tejal A. Desai
doi: https://doi.org/10.1101/2021.11.22.469570
Joel A. Finbloom
1Department of Bioengineering and Therapeutic Sciences. University of California, San Francisco. San Francisco, CA, USA
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  • ORCID record for Joel A. Finbloom
  • For correspondence: Joel.Finbloom@ucsf.edu Michelle.Yu2@ucsf.edu Tejal.Desai@ucsf.edu
Preethi Raghavan
1Department of Bioengineering and Therapeutic Sciences. University of California, San Francisco. San Francisco, CA, USA
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Bhushan N. Kharbikar
1Department of Bioengineering and Therapeutic Sciences. University of California, San Francisco. San Francisco, CA, USA
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Michelle A. Yu
2Division of Pulmonary and Critical Care Medicine. University of California, San Francisco. San Francisco, CA, USA
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  • For correspondence: Joel.Finbloom@ucsf.edu Michelle.Yu2@ucsf.edu Tejal.Desai@ucsf.edu
Tejal A. Desai
1Department of Bioengineering and Therapeutic Sciences. University of California, San Francisco. San Francisco, CA, USA
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  • For correspondence: Joel.Finbloom@ucsf.edu Michelle.Yu2@ucsf.edu Tejal.Desai@ucsf.edu
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Abstract

New approaches are needed to treat bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA). PA biofilms have high rates of antimicrobial resistance and are commonly found in chronic wound and cystic fibrosis lung infections. The use of combination therapeutics that act synergistically is a promising treatment strategy; however, the delivery of multiple therapeutics at relevant dosages is challenging in the clinic. We therefore developed a new nanoscale drug carrier by combining approaches from both polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers functionalized with both tobramycin antibiotics and antimicrobial silver nanoparticles with high loading efficiencies. AgTob-NCs displayed synergistic enhancements in antimicrobial activity against planktonic and biofilm PA cultures, with positively charged NCs demonstrating complete biofilm eradication. Overall, this approach shows promise in the co-delivery of diverse classes of antimicrobials to overcome antimicrobial resistance and treat bacterial biofilm infections.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 22, 2021.
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Polyelectrolyte Nanocomplex Formation Combined with Electrostatic Self-Assembly Enables the Co-Delivery of Synergistic Antimicrobials to Treat Bacterial Biofilms
Joel A. Finbloom, Preethi Raghavan, Bhushan N. Kharbikar, Michelle A. Yu, Tejal A. Desai
bioRxiv 2021.11.22.469570; doi: https://doi.org/10.1101/2021.11.22.469570
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Polyelectrolyte Nanocomplex Formation Combined with Electrostatic Self-Assembly Enables the Co-Delivery of Synergistic Antimicrobials to Treat Bacterial Biofilms
Joel A. Finbloom, Preethi Raghavan, Bhushan N. Kharbikar, Michelle A. Yu, Tejal A. Desai
bioRxiv 2021.11.22.469570; doi: https://doi.org/10.1101/2021.11.22.469570

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