Hyaluronic acid-based nanogels improve in vivo compatibility of the anti-biofilm peptide DJK-5

• Published in: Nanomedicine Vol. 20; p. 102022
• Main Authors: Kłodzińska, Sylvia N., Pletzer, Daniel, Rahanjam, Negin, Rades, Thomas, Hancock, Robert E.W., Nielsen, Hanne M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019
• Subjects: Abscess - pathology; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biofilm; Biofilms - drug effects; Cationic peptide; Drug delivery; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Mice; Nanogel; Nanogels - chemistry; Nanogels - ultrastructure; Oligopeptides - chemistry; Oligopeptides - pharmacology; Pseudomonas aeruginosa; Reactive Nitrogen Species - metabolism; Reactive Oxygen Species - metabolism; Skin - drug effects; Subcutaneous Tissue - drug effects; Subcutaneous Tissue - pathology; Biofilm; Pseudomonas aeruginosa; Drug delivery; Nanogel; Cationic peptide
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2019.102022

Anti-biofilm peptides are a subset of antimicrobial peptides and represent promising broad-spectrum agents for the treatment of bacterial biofilms, though some display host toxicity in vivo. Here we evaluated nanogels composed of modified hyaluronic acid for the encapsulation of the anti-biofilm peptide DJK-5 in vivo. Nanogels of 174 to 194 nm encapsulating 33–60% of peptide were created. Efficacy and toxicity of the nanogels were tested in vivo employing a murine abscess model of a Pseudomonas aeruginosa LESB58 high bacterial density infection. The dose of DJK-5 that could be administered intravenously to mice without inducing toxicity was more than doubled after encapsulation in nanogels. Upon subcutaneous administration, the toxicity of the DJK-5 in nanogels was decreased four-fold compared to non-formulated peptide, without compromising the anti-abscess effect of DJK-5. These findings support the use of nanogels to increase the safety of antimicrobial and anti-biofilm peptides after intravenous and subcutaneous administration. The antibiofilm peptide DJK-5 was encapsulated in nanogels composed of octenyl succinic anhydride-modified hyaluronic acid to reduce the toxicity of the peptide. The loaded nanogels were visualized using TEM, while the toxicity and antimicrobial activity was assessed in a murine abscess model. The results show that encapsulation of this peptide in nanogels reduces the peptide's toxicity, maintains antimicrobial activity and provides an immunostimulatory effect. [Display omitted]