Combined antimicrobial and pro-healing effects of cathelicidins in a polysaccharide-based hydrogel scaffold: treatment of carbapenemase-resistant Pseudomonas aeruginosa wound infections in a porcine model

  • Int J Pharm. 2026 Jun 25:699:126992. doi: 10.1016/j.ijpharm.2026.126992.
Antonín Pavelka  1 ,  Břetislav Lipový  2 ,  Lubomír Janda  3 ,  Jana Brtníková  4 ,  Martin Knoz  5 ,  Jakub Holoubek  6 ,  Vladimír Váňa  7 ,  Edita Jeklová  3 ,  Petra Straková  3 ,  Peter Makovický  8 ,  Marko Šefranko  9 ,  Dominika Polaštík Kleknerová  9 ,  Frederik Volný  9 ,  Ivana Chamradová  4 ,  Lucy Vojtová  4 ,  Filip Růžička  9 ,  Lukáš Vacek  10
Affiliations
  • 1. Infectious diseases and preventive medicine, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
  • 2. Department of Burns Medicine, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Šrobárova 50, 100 34 Prague, Czech Republic; Advanced Biomaterials Group, Central European Institute of Technology, Brno University of Technology, Purkyňova 656/123, 612 00 Brno, Czech Republic.
  • 3. Infectious diseases and preventive medicine, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
  • 4. Advanced Biomaterials Group, Central European Institute of Technology, Brno University of Technology, Purkyňova 656/123, 612 00 Brno, Czech Republic.
  • 5. Clinic of plastic and esthetic surgery, St Anne's University Hospital, Pekařská 664/53, 602 00 Brno, Czech Republic.
  • 6. Department of Traumatology, Faculty of Medicine, Masaryk University, Ponávka 139/6, 602 00 Brno, Czech Republic.
  • 7. Department of Burns and Plastic Surgery, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
  • 8. Infectious diseases and preventive medicine, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic; Department of Histology and Embryology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava-Vítkovice, Czech Republic.
  • 9. Department of Microbiology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 602 00 Brno, Czech Republic.
  • 10. Department of Microbiology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 602 00 Brno, Czech Republic. Electronic address: [email protected].
PMID: 42150643 DOI: 10.1016/j.ijpharm.2026.126992
Abstract

Given the global rise in Antibiotic resistance, this study focuses on developing an alternative treatment for deep skin and soft tissue infections (SSTIs) caused by a carbapenem-resistant Pseudomonas aeruginosa. An injectable hydrogel composed of polyvinyl alcohol and chitosan was developed as a stable carrier for the porcine cathelicidins PR-39 and Protegrin-1. In vitro tests demonstrated that the addition of 8 mM EDTA fully restores the activity of Antibacterial peptides in fetal bovine serum and eliminates the influence of divalent cations. In a porcine model, the application of this hydrogel resulted in a significant reduction in Bacterial load after only two doses, with levels dropping below 105 CFU/g of tissue. In addition to eliminating the Infection, the treated group showed early granulation tissue formation, reduced necrosis and inflammation, and the development of a continuous epidermis, all of which were completely absent in the untreated group. The research confirms that the combination of cathelicidins and EDTA in a hydrogel carrier represents a highly effective approach for treating complicated Bacterial infections.

Keywords
Antimicrobial peptides; CRPA; Carbapenem-resistant Pseudomonas aeruginosa; Chitosan; EDTA; PR-39; Protegrin-1.
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