Due to increasing resistance development against conventional antibiotics, antimicrobial peptides (AMPs) are receiving considerable attention as potential therapeutics. Through lysis of bacterial membranes, AMPs provide fast and broad-spectrum antimicrobial effects. While there have been considerable efforts to identify potent and selective AMPs, drug delivery aspects of such compounds have been less studied. For example, infected tissue is often characterized by high proteolytic activity. Thus, administration of AMPs is likely to result in rapid degradation of the peptide and corresponding activity loss. Furthermore AMPs bind to serum proteins and are rapidly cleared from bloodstream, which can translate into reduced efficacy, as well as toxicity effects, related to accumulation in the reticuloendothelial system. In these and other contexts, it would be advantageous to combine AMPs with delivery systems designed for the application at hand.<br/><br/>Microgels are lightly cross-linked polymer colloids, displaying dramatic volume transitions in response to different stimuli. They are of particularly interest as carriers for biomacromolecular drugs since they offer a water-rich environment, thus reducing detrimental conformational changes, at the same time as providing protection against enzymatic degradation and allowing controlled or triggered release. In order to elucidate key properties of AMP-loaded microgels, we here investigate effects of microgel charge density on AMP loading and release, using a library of poly(ethyl acrylate-co-methacrylic acid) microgels, investigated with ellipsometry, particle size- and z-potential measurements. In addition, membrane interactions of peptide-loaded microgels are addressed, translating from biophysical studies with ellipsometry and liposome leakage to investigations of functional consequences, including antimicrobial activitity, cell toxicity and proteolytic stability.

Poly(acrylic acid) microgels as carriers for antimicrobial peptides

255th National Meeting (2018)

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