Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath
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Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath. / van Gent, Miriam E.; Kłodzińska, Sylvia N.; Severin, Maureen; Ali, Muhanad; van Doodewaerd, Bjorn R.; Bos, Erik; Koning, Roman I.; Drijfhout, Jan Wouter; Nielsen, Hanne M.; Nibbering, Peter H.
I: Nanomedicine: Nanotechnology, Biology, and Medicine, Bind 52, 102694, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath
AU - van Gent, Miriam E.
AU - Kłodzińska, Sylvia N.
AU - Severin, Maureen
AU - Ali, Muhanad
AU - van Doodewaerd, Bjorn R.
AU - Bos, Erik
AU - Koning, Roman I.
AU - Drijfhout, Jan Wouter
AU - Nielsen, Hanne M.
AU - Nibbering, Peter H.
N1 - Funding Information: The authors acknowledge financial support from the Dutch Research Council (NWO), Novel Antibacterial Compounds and Therapies Antagonizing Resistance Program: grant number 16434 . S.N.K. and H.M.N. were supported by the Novo Nordisk Foundation , Grand Challenge Program: NNF16OC0021948 .
PY - 2023
Y1 - 2023
N2 - The antimicrobial peptide Ab-Cath, is a promising candidate for development as treatment for antimicrobial resistant (AMR) bacterial infections. Future clinical use is hampered by Ab-Cath's cationic peptidic nature and limited therapeutic window. Here, we evaluated hyaluronic acid-based nanogels for encapsulation of Ab-Cath to circumvent these limitations. Using microfluidics, monodispersed anionic nanogels of 156–232 nm encapsulating >99 % Ab-Cath were prepared. Unprecedented, lyophilization using polyvinyl alcohol and dextran-40 provided Ab-Cath nanogel protection and allowed easy dose adjustment. Lyophilized and redispersed Ab-Cath nanogels were as effective as Ab-Cath solution in killing AMR Staphylococcus aureus, Acinetobacter baumannii and Escherichia coli in biological fluids, and in reducing S. aureus and A. baumannii biofilms. Importantly, encapsulation of Ab-Cath in nanogels reduced Ab-Cath's cytotoxic effects on human fibroblasts by ≥10-fold. Moreover, cutaneous application of Ab-Cath nanogels eliminated bacteria colonizing 3D human skin. These findings affirm the use of nanogels to increase the selectivity index of antimicrobial peptides.
AB - The antimicrobial peptide Ab-Cath, is a promising candidate for development as treatment for antimicrobial resistant (AMR) bacterial infections. Future clinical use is hampered by Ab-Cath's cationic peptidic nature and limited therapeutic window. Here, we evaluated hyaluronic acid-based nanogels for encapsulation of Ab-Cath to circumvent these limitations. Using microfluidics, monodispersed anionic nanogels of 156–232 nm encapsulating >99 % Ab-Cath were prepared. Unprecedented, lyophilization using polyvinyl alcohol and dextran-40 provided Ab-Cath nanogel protection and allowed easy dose adjustment. Lyophilized and redispersed Ab-Cath nanogels were as effective as Ab-Cath solution in killing AMR Staphylococcus aureus, Acinetobacter baumannii and Escherichia coli in biological fluids, and in reducing S. aureus and A. baumannii biofilms. Importantly, encapsulation of Ab-Cath in nanogels reduced Ab-Cath's cytotoxic effects on human fibroblasts by ≥10-fold. Moreover, cutaneous application of Ab-Cath nanogels eliminated bacteria colonizing 3D human skin. These findings affirm the use of nanogels to increase the selectivity index of antimicrobial peptides.
KW - AMR infection
KW - Antimicrobial peptide Ab-Cath
KW - Drug delivery
KW - Lyophilization method
KW - Nanogel
U2 - 10.1016/j.nano.2023.102694
DO - 10.1016/j.nano.2023.102694
M3 - Journal article
C2 - 37394107
AN - SCOPUS:85164280040
VL - 52
JO - Nanomedicine: Nanotechnology, Biology and Medicine
JF - Nanomedicine: Nanotechnology, Biology and Medicine
SN - 1549-9634
M1 - 102694
ER -
ID: 360246744