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 -