Antimicrobial Loaded Graft-Copolymer Nanoparticles for Treatment of Pseudomonas aeruginosa Infections

Yadiel Varela Soler1, William Xu2, Mariana R N Lima3

  • 1Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, United States.

Insights

New polyelectrolyte surfactants effectively encapsulate cationic antimicrobials. These nanoparticles show enhanced activity against planktonic Pseudomonas aeruginosa, offering a promising strategy for cystic fibrosis lung infections.

Area of Science:

  • Biomaterials Science
  • Infectious Diseases
  • Nanotechnology

Background:

  • Cystic fibrosis (CF) patients frequently suffer from persistent lung infections, primarily by Pseudomonas aeruginosa.
  • P. aeruginosa forms biofilms that impede antimicrobial efficacy due to interactions with anionic compounds in mucus and biofilms.
  • Developing novel drug delivery systems is crucial to overcome treatment challenges in CF lung infections.

Purpose of the Study:

  • To investigate polyelectrolyte surfactants for nanoencapsulation and delivery of cationic antimicrobials.
  • To assess the impact of surfactant structure on nanoparticle properties and antimicrobial activity.
  • To evaluate nanoformulations against planktonic and biofilm P. aeruginosa from clinical isolates.

Main Methods:

  • Synthesized anionic poly(alkylacrylic acid) backbone with grafted polyetheramine chains as polyelectrolyte surfactants.
  • Formulated nanoparticles by self-assembly of surfactants with cationic antimicrobials.
  • Assessed nanoparticle encapsulation efficiency, physical properties, and antimicrobial activity against P. aeruginosa.
  • Monitored bacterial membrane potential and nanoparticle uptake.

Main Results:

  • All synthesized surfactants effectively encapsulated cationic antimicrobials, correlating with hydrophilic-lipophilic balance.
  • Nanoformulations significantly enhanced antimicrobial activity against planktonic P. aeruginosa.
  • Antimicrobial activity against P. aeruginosa biofilms was retained but not increased by the nanoformulations.
  • Nanoparticles were observed to associate directly with bacterial cell membranes.

Conclusions:

  • Polyelectrolyte surfactants can be designed for effective nanoencapsulation of cationic drugs.
  • The developed nanoformulations show potential for improved delivery against planktonic P. aeruginosa infections.
  • This approach offers a proof of concept for novel antimicrobial delivery systems in challenging infections like those in cystic fibrosis.