Pseudomonas aeruginosa pyocyanin production reduced by quorum-sensing inhibiting nanocarriers

Hoang D. Lu, Elizabeth Pearson, Kurt D. Ristroph, Gregg A. Duncan, Laura M. Ensign, Jung Soo Suk, Justin Hanes, Robert K. Prud'homme

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Pseudomonas aeruginosa is an opportunistic gram-negative pathogen that causes a wide range of infections; it is becoming increasingly difficult to treat due to antibiotic resistance. Quorum-sensing (QS) based therapeutics, which function by disabling pathogen virulence without killing pathogens, are a promising class of drugs that may be used to treat bacterial infections without eliciting resistance development. The use of QS drugs to treat pulmonary P. aeruginosa infections, however, has been greatly limited due to the inability to deliver QS drugs at sufficiently high concentrations past physiological barriers such as pulmonary mucus. Here we apply a block copolymer-directed self-assembly process, Flash NanoPrecipitation, to develop a series of QS-active formulations that are fully water dispersible, stable, and mucus-penetrating. These formulations inhibit P. aeruginosa virulence without inhibiting cell growth. Particle size (70 nm–400 nm) and release rate (1 h–14 days) can be tuned by altering constructs’ physical properties and formulation excipients. We also demonstrate, to the best of our knowledge, the first instance of a QS nanocarrier platform technology that can penetrate through human cystic fibrosis pulmonary mucus. This work highlights the need to incorporate nanoformulation strategies into the development of next-generation antimicrobial therapeutics.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume544
Issue number1
DOIs
StatePublished - Jun 10 2018

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Drug-delivery
  • Mucus penetration
  • Nanocarrier
  • Nanoparticle
  • Pseudomonas aeruginosa
  • Quorum sensing

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