(197a) The Triggered Delivery of Polymyxin Antibiotics from Polyelectrolyte Microgels
AIChE Annual Meeting
Monday, November 8, 2021 - 3:30pm to 3:48pm
With the objective of creating self-defensive surfaces using FDA-approved antibiotics, we are working to identify the key properties that control microgel/antibiotic complexation and, thus, the ability of microgels to sequester and release their antibiotic payload. Here we focus on polymyxin B and E and their complexation with poly(styrene sulfonate) (PSS) microgels. We follow loading and sequestration using time-resolved optical microscopy to measure microgel deswelling/swelling in a continuous flow chamber that provides precise control over pH, ionic strength, and antibiotic concentration. Recent work (2) has shown that the PSS/colistin complexation strength is greater than the PAA/colistin complexation strength, an effect demonstrated by coarse-grain molecular dynamics simulations to be caused by the presence of the pendant phenyl rings along the PSS backbone. Except for a phenyl ring that substitutes for a dimethyl group, polymyxin B is chemically identical to colistin, yet we find that the threshold [Na+] in phosphate buffer to trigger release (de-complexation) is 0.216 M for colistin and 0.516 M for polymyxin B release, again indicating that aromaticity plays an important role in complexation and antibiotic sequestration. This finding has important implications on how each of these antibiotics might be incorporated into a self-defensive technology, and work continues to assess the interactions of polymyxin-loaded PSS microgels with gram-negative bacteria.
(1) J. Liang, H. Wang, and M. Libera, Biomaterial Surfaces Self-Defensive against Bacteria by Contact Transfer of Antimicrobials.Biomaterials, 2019. 204(June): p. 25-35.
(2) X. Xiao, J. Ji, W. Zhao, S. Nangia, and M. Libera. Salt Destabilization of the Complexation of Cationic Colistin within Polyanionic Microgels, submitted to Macromolecules, 2021.