Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath
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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.
|Journal||Nanomedicine: Nanotechnology, Biology, and Medicine|
|Number of pages||11|
|Publication status||Published - 2023|
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 .
- AMR infection, Antimicrobial peptide Ab-Cath, Drug delivery, Lyophilization method, Nanogel