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Published on: February 27, 2019
Biopolymer Nano-Network for Antimicrobial Peptide Protection and Local Delivery
Natthaporn Klubthawee1, Giovanni Bovone2, Bruno Marco-Dufort2
1Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, 12120, Thailand.
Abstract:
Antimicrobial resistance (AMR) develops when bacteria no longer respond to conventional antimicrobial treatment. The limited treatment options for resistant infections result in a significantly increased medical burden. Antimicrobial peptides offer advantages for treatment of resistant infections, including broad-spectrum activity and lower risk of resistance development. However, sensitivity to proteolytic cleavage often limits their clinical application. Here, a moldable and biodegradable colloidal nano-network is presented that protects bioactive peptides from enzymatic degradation and delivers them locally. An antimicrobial peptide, PA-13, is encapsulated electrostatically into positively and negatively charged nanoparticles made of chitosan and dextran sulfate without requiring chemical modification. Mixing and concentration of oppositely charged particles form a nano-network with the rheological properties of a cream or injectable hydrogel. After exposure to proteolytic enzymes, the formed nano-network loaded with PA-13 eliminates Pseudomonas aeruginosa during in vitro culture and in an ex vivo porcine skin model while the unencapsulated PA-13 shows no antibacterial effect. This demonstrates the ability of the nano-network to protect the antimicrobial peptide in an enzyme-challenged environment, such as a wound bed. Overall, the nano-network presents a useful platform for antimicrobial peptide protection and delivery without impacting peptide bioactivity.
Insights
A novel nano-network protects antimicrobial peptides from degradation, effectively eliminating resistant bacteria like Pseudomonas aeruginosa in wound models. This breakthrough offers a promising new strategy for treating challenging infections.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Microbiology
Background:
- Antimicrobial resistance (AMR) poses a significant global health threat due to limited treatment options.
- Antimicrobial peptides (AMPs) show promise for treating resistant infections but are often degraded by enzymes.
- Developing effective delivery systems for AMPs is crucial for clinical applications.
Purpose of the Study:
- To develop a moldable, biodegradable nano-network for protecting and delivering antimicrobial peptides.
- To evaluate the efficacy of the nano-network in protecting an antimicrobial peptide from enzymatic degradation.
- To assess the antibacterial activity of the peptide-loaded nano-network against Pseudomonas aeruginosa.
Main Methods:
- An antimicrobial peptide (PA-13) was electrostatically encapsulated into chitosan and dextran sulfate nanoparticles.
- Oppositely charged nanoparticles were mixed to form a nano-network with cream/hydrogel properties.
- The nano-network's ability to protect PA-13 from proteolytic enzymes was tested in vitro and in an ex vivo porcine skin model.
Main Results:
- The nano-network successfully protected PA-13 from enzymatic degradation.
- The PA-13-loaded nano-network eliminated Pseudomonas aeruginosa in vitro and in an ex vivo porcine skin model.
- Unencapsulated PA-13 showed no antibacterial effect under the same conditions, highlighting the nano-network's protective function.
Conclusions:
- The developed nano-network is an effective platform for protecting antimicrobial peptides from enzymatic degradation.
- This system enables local delivery of functional antimicrobial peptides, even in enzyme-rich environments like wound beds.
- The nano-network shows potential for advancing the treatment of antimicrobial-resistant infections without compromising peptide bioactivity.

