Polymersome‐Enabled Multimodal Delivery of Tobramycin and Doripenem for Targeted Eradication of Pseudomonas aeruginosa Biofilms in Chronic Rhinosinusitis
5 affiliations
- 1Department of Health Technology Technical University of Denmark Lyngby Denmark
- 2Department of Biomedical Engineering, Institute for Complex Molecular Systems Eindhoven University of Technology Eindhoven The Netherlands
- 3Department of Biotechnology and Biomedicine, Section for Microbial and chemical ecology Technical University of Denmark Lyngby Denmark
- 4Department of Clinical Microbiology, Rigshospitalet Copenhagen University Hospital Copenhagen Ø Denmark
- 5Department of Immunology and Microbiology Costerton Biofilm Center University of Copenhagen Copenhagen Denmark
Abstract
Biofilms formed by Pseudomonas aeruginosa pose a major therapeutic challenge due to limited antibiotic penetration and increased tolerance. Here, we present a polymersome‐based platform designed to enable biofilm penetration and controlled antibiotic release. pH‐responsive polymersomes (∼100 nm, PEG‐p(CL‐g‐TMCimid.)) were prepared by incorporating imidazole groups into the hydrophobic block of an amphiphilic copolymer, allowing rapid disassembly and tobramycin (TOB) release under mildly acidic conditions characteristic of the biofilm microenvironment. In parallel, inert PEG‐p(CL‐g‐TMC) polymersomes were used to achieve sustained release of doripenem (DOR). Quartz crystal microbalance with dissipation (QCM‐D) monitoring demonstrated reversible interactions between polymersomes and alginate, a key component of the biofilm matrix, supporting their ability to penetrate the extracellular polymeric substance (EPS). All polymersome formulations were well tolerated by nasal epithelial cells. Antibiofilm efficacy was evaluated against mature P. aeruginosa biofilms under flow conditions. pH‐responsive blank polymersomes exhibited pronounced intrinsic antibiofilm activity, exceeding that of antibiotic‐loaded monotherapies and bolus antibiotic administration. Notably, co‐dosing with pH‐responsive polymersomes and DOR‐loaded inert polymersomes resulted in the most effective biofilm eradication. Overall, the results demonstrate that the pH‐responsive polymersome carrier contributes substantially to antibiofilm activity, while sustained DOR delivery may further enhance therapeutic efficacy against biofilm‐associated infections.
Related
- High-Entropy Alloy-Engineered ZnIn2S4 Photocatalyst for Efficient In Vitro Eradication of MRSA and Inhibition of Biofilm Formation via ROS-Mediated Mechanisms
- Metagenomic and Metabolomic Signatures of Gut Microbiota After Helicobacter pylori Eradication Therapy Supplemented with Butyric Acid and Inulin: Observational Study.
- Optimization of Antibiotic and Antimycotic Compositions for the Eradication of Microorganisms from Cell Cultures.
- Widely Targeted Lipidomics of Nasal Fluid Across Upper-Airway Inflammation: Phenotype-Associated Remodeling in Allergic Rhinitis and Chronic Rhinosinusitis with Nasal Polyps
- Expression of ExsA in trans Confers Type III Secretion System-Dependent Cytotoxicity on Noncytotoxic Pseudomonas aeruginosa Cystic Fibrosis Isolates
BibTeX
@article{andresen2026polymersomeenabled,
title = {{Polymersome‐Enabled Multimodal Delivery of Tobramycin and Doripenem for Targeted Eradication of Pseudomonas aeruginosa Biofilms in Chronic Rhinosinusitis}},
author = {Amalie Kjær Andresen and Matteo Tollemeto and Alexander B. Cook and Claus Sternberg and Yudong Li and Claus Moser and Lars Jelsbak and Jan C. M. Van Hest and Anja Boisen and Line Hagner Nielsen},
journal = {Small (Weinheim an Der Bergstrasse, Germany)},
year = {2026},
month = jul,
doi = {10.1002/smll.74703},
url = {https://doi.org/10.1002/smll.74703},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Polymersome‐Enabled Multimodal Delivery of Tobramycin and Doripenem for Targeted Eradication of Pseudomonas aeruginosa Biofilms in Chronic Rhinosinusitis
AU - Amalie Kjær Andresen
AU - Matteo Tollemeto
AU - Alexander B. Cook
AU - Claus Sternberg
AU - Yudong Li
AU - Claus Moser
AU - Lars Jelsbak
AU - Jan C. M. Van Hest
AU - Anja Boisen
AU - Line Hagner Nielsen
PY - 2026
DA - 2026/07/22
JO - Small (Weinheim an Der Bergstrasse, Germany)
DO - 10.1002/smll.74703
UR - https://doi.org/10.1002/smll.74703
AB - Biofilms formed by Pseudomonas aeruginosa pose a major therapeutic challenge due to limited antibiotic penetration and increased tolerance. Here, we present a polymersome‐based platform designed to enable biofilm penetration and controlled antibiotic release. pH‐responsive polymersomes (∼100 nm, PEG‐p(CL‐g‐TMCimid.)) were prepared by incorporating imidazole groups into the hydrophobic block of an amphiphilic copolymer, allowing rapid disassembly and tobramycin (TOB) release under mildly acidic conditions characteristic of the biofilm microenvironment. In parallel, inert PEG‐p(CL‐g‐TMC) polymersomes were used to achieve sustained release of doripenem (DOR). Quartz crystal microbalance with dissipation (QCM‐D) monitoring demonstrated reversible interactions between polymersomes and alginate, a key component of the biofilm matrix, supporting their ability to penetrate the extracellular polymeric substance (EPS). All polymersome formulations were well tolerated by nasal epithelial cells. Antibiofilm efficacy was evaluated against mature P. aeruginosa biofilms under flow conditions. pH‐responsive blank polymersomes exhibited pronounced intrinsic antibiofilm activity, exceeding that of antibiotic‐loaded monotherapies and bolus antibiotic administration. Notably, co‐dosing with pH‐responsive polymersomes and DOR‐loaded inert polymersomes resulted in the most effective biofilm eradication. Overall, the results demonstrate that the pH‐responsive polymersome carrier contributes substantially to antibiofilm activity, while sustained DOR delivery may further enhance therapeutic efficacy against biofilm‐associated infections.
SN - 1613-6810
SN - 1613-6829
ER -