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

Publication date: Available online 4 June 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Sylvia N. Kłodzińska, Daniel Pletzer, Negin Rahanjam, Thomas Rades, Robert E.W. Hancock, Hanne M. NielsenAbstractAnti-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.Graphical AbstractThe 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 u...

Source: Nanomedicine: Nanotechnology, Biology and Medicine - June 4, 2019 Category: Nanotechnology Source Type: research