(358f) The Effects of Aromaticity on Antimicrobial Delivery from Polyelectrolyte Microgels | AIChE

(358f) The Effects of Aromaticity on Antimicrobial Delivery from Polyelectrolyte Microgels


Xiao, X. - Presenter, Stevens Institute of Technology
Libera, M., Stevens Institute of Technology
Zhao, W., Steven Institute of Technology
Micron-sized hydrogels (microgels) are attractive vehicles for the delivery of drugs owing to their capability to load and locally release cargoes responsively. In particular, polyanionic microgels introduce noncovalent electrostatic interactions able to complex and sequester oppositely charged antibiotics. We have found, for example, that poly(acrylic acid) (PAA) microgels can be electrodeposited onto solid surfaces, then loaded by complexation with cationic antimicrobial peptides, and sequester those peptides until a bacterial challenge triggers their release by a mechanism referred to as contact transfer [1]. A key challenge is to better understand the strength of the microgel-antimicrobial complexation interaction to broaden the range of cationic antimicrobials that can be used within this delivery platform. Notably, under physiological conditions, the complexation can in some cases be broken by salt screening. Our previous work, for example, showed that PAA microgels can sequester complexed colistin, an FDA-approved antibiotic, in 0.01M phosphate buffer for 30 days. However, in PBS with an ionic strength of 0.14 M the complexation is interrupted, and colistin undergoes a rapid burst release. To enhance the complexation strength, we are exploring alternative microgel chemistries including using sulfonates rather than carboxylates. We have made poly(styrene sulfonate) (PSS) microgels by suspension photopolymerization of styrene sulfonate. In addition to the sulfonic acid group, PSS brings aromaticity that can participate in the complexation reaction by cation- binding. We follow the time-resolved microgel deswelling during complexation loading as well as the microgel reswelling during release in buffers with controlled ionic strength by in situ optical microscopy. PSS microgels de-swell when complexed with colistin. We furthermore found that PSS microgel can sequester colistin in static PBS buffer for more than 18 hours, whereas it releases over a time scale of minutes from PAA under similar conditions. To further separate the effects of aromaticity from those of the sulfonate group in PSS, poly(vinyl sulfonate-co-styrene sulfonate) microgels were synthesized. We find that decreasing the amount of aromatic sulfonate substantially increases the rate of colistin release indicating that colistin interactions with aromatic rings within the microgel significantly enhance the complexation strength. We have found a similar enhancement in non-aromatic microgel systems (e.g. PAA) when the antimicrobial includes aromatic moieties (e.g. polymyxin B). Ongoing work focuses on the mechanism of how aromaticity strengthens the complexation as well as how to optimize the microgel chemistry in order to achieve long-term sequestration of FDA-approved antibiotics under physiological conditions.

[1] Liang, Jing, Hongjun Wang, and Matthew Libera. "Biomaterial surfaces self-defensive against bacteria by contact transfer of antimicrobials." Biomaterials 204 (2019): 25-35.