Antimicrobial Loaded Graft-Copolymer Nanoparticles for Treatment of Pseudomonas aeruginosa Infections
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Evaluation of Antimicrobial Activities of Nanoparticles and Nanostructured Surfaces In Vitro
Published on: April 21, 2023
Yadiel Varela Soler1, William Xu2, Mariana R N Lima3
1Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, United States.
Abstract:
Nearly 80% of cystic fibrosis patients are affected by persistent lung infections, with Pseudomonas aeruginosa being one of the major culprits. Treatment of P. aeruginosa is further complicated by its ability to form biofilms. Anionic compounds within the biofilm and thick cystic fibrosis mucus interact with cationic antimicrobials, hindering treatment efficacy. In this study, we investigated the treatment of lung infections by delivering antimicrobials via polyelectrolyte surfactants that are composed of an anionic poly(alkylacrylic acid) backbone with grafted polyetheramine pendent chains. When combined with cationic antimicrobials, they selfassemble into nanoparticles via electrostatic interactions. We assessed the role of backbone chemistry and graft density on nanoparticle physical properties and evaluated the antimicrobial activity of these formulations against planktonic and biofilm cultures of P. aeruginosa strains derived from clinical isolates. All synthesized polyelectrolyte surfactants demonstrated high levels of antimicrobial encapsulation, with the extent of drug bound corresponding to the calculated hydrophilic-lipophilic balance values. We observed significantly increased antimicrobial activity against planktonic cultures using nanoformulations containing one of the polyelectrolyte surfactants, PMAA-g-10%J. In contrast, all tested nanoformulations retained, but did not increase, activity against biofilms. By monitoring membrane potentials and nanoparticle uptake, it was found that the nanoparticles directly associate with the bacterial cell membranes, which may enhance drug delivery and underlie the improved activity against the planktonic bacteria. In conclusion, we provide a proof of concept for the design of polyelectrolyte surfactants for the nanoencapsulation and delivery of cationic drug cargoes against P. aeruginosa infections.
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.

