Various strategies have been applied to inhibit chronic infection associated with tissue-contacting biomedical devices. Traditional drug delivery based on the elution of antimicrobials from has been extensively explored. However, this method often releases its loaded antimicrobials before being challenged by bacteria. Here, we demonstrate an approach that first modifies a synthetic surface with anionic microgels and subsequently loads them by complexation with cationic antimicrobials. Significantly, these complexed antimicrobials can be sequestered for extended time periods including in particular cases multiple weeks under physiological condition appropriate for combating bacterial colonization of implanted biomedical devices.<br/><br/>Lightly crosslinked poly(acrylic acid) microgels were electrostatically deposited onto poly(allyamine hydrochloride)-primed glass substrates and their response to various solution conditions was followed by <i>in situ </i>optical and confocal microscopy. The osmotic swelling of microgels was observed in neutralized low ionic strength buffers. The addition of cationic antimicrobials (e.g. colistin, L5, Sub 5) led to microgel deswelling because of antimicrobial-microgel complexation. By eluting the antimicrobial-complexed microgels into buffers with varying pH and ionic strength, the stabilization of antimicrobial-microgel complexation was studied. Microgel reswelling indicated antimicrobial elution into the surrounding buffer. In general, high ionic strength and low pH usually result in a rapid release of antimicrobials. Moreover, the loading and release of cationic antimicrobials with different physiochemical properties (molecular weight, charge density, hydrophobicity) was studied. For small cationic antibiotics, complexation loading was rapid and within one minute. However, they released rapidly under physiological ionic strength and pH. For larger antimicrobial peptides with more hydrophobicity, the loading process took longer and resulted in more stable complexation able to resist elution into physiological buffer. Antimicrobials with higher charge density also showed stronger complexation and could be sequestered within the microgels for 30 days under physiological conditions. Despite being strongly complexed within the microgels, these antimicrobial-loaded microgel-modified surfaces were able to resist bacterial colonization by actively killed bacteria.

Complexation loading of antimicrobial peptides into microgel-modified surfaces

256th National Meeting (2018)

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