Biopolymer Nano‐Network for Antimicrobial Peptide Protection and Local Delivery

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.

Self-Healing Injectable Hydrogels for Tissue Regeneration

“…By employing reversible noncovalent interparticle interactions, gelatin nanoparticles have been assembled, with or without other particle types, into dynamic colloidal gel networks. ,,,,,,,, Covalently cross-linked hyaluronic acid-based microgels were fabricated and jammed to form self-healing injectable granular hydrogels based on reversible interparticle host–guest, hydrazone, or metal coordination interactions . Chitosan can also be aggregated into spherical microgels or nanogels to form granular hydrogels, which have been used as injectable tissue scaffolds and drug delivery vehicles. − Recent findings suggest that altering the morphology of the microgel building blocks allows tuning of the properties of resulting granular hydrogels. , …”

The Year 2022 in biomaterials research: A perspective from the editors of six leading journals

“…The authors employ cell‐laden hydrogels that could be precisely patterned via water‐soluble gelatin templates that are constructed by economical extrusion 3D printed plastic templates. Secondly, the groups of Ratchaneewan Aunpad (Thammasat University, Thailand) and Mark W. Tibbitt (ETH Zurich, Switzerland) report on a novel biopolymer nano‐network for antimicrobial peptide delivery 19 . This material is made of electrostatically encapsulated peptides within positively and negatively charged nanoparticles made of chitosan and dextran sulfate without further chemical modification.…”

“…The contributions in this paper will also be presented and discussed during a panel session of the editors at the 2023 Annual Meeting of the Society for Biomaterials in San Diego (April [19][20][21][22]2023).…”

Antimicrobial Peptides: From Design to Clinical Application

“…For example, AMPs are sensitive to prote enzymes, which limits their application. Post-exposure to proteolytic enzymes, formed PA-13 that was encapsulated electrostatically into nanoparticles kept their k activity against P. aeruginosa both for in vitro culture and ex vivo skin model in po However, unencapsulated PA-13 lost antimicrobial activity [129]. In addition, nan struction can be applied to design nontoxic AMPs [130].…”