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

TY - JOUR

T1 - Hyaluronic acid-based nanogels improve in vivo compatibility of the anti-biofilm peptide DJK-5

AU - Kłodzińska, Sylvia N.

AU - Pletzer, Daniel

AU - Rahanjam, Negin

AU - Rades, Thomas

AU - Hancock, Robert E.W.

AU - Nielsen, Hanne M.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Biofilm

KW - Cationic peptide

KW - Drug delivery

KW - Nanogel

KW - Pseudomonas aeruginosa

U2 - 10.1016/j.nano.2019.102022

DO - 10.1016/j.nano.2019.102022

M3 - Journal article

C2 - 31170510

AN - SCOPUS:85068142260

SN - 1549-9634

VL - 20

JO - Nanomedicine: Nanotechnology, Biology and Medicine

JF - Nanomedicine: Nanotechnology, Biology and Medicine

M1 - 102022

ER -