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. 2018 Feb 23;3(2):186-193.
doi: 10.1016/j.bioactmat.2018.02.001. eCollection 2018 Jun.

Facially amphiphilic polyionene biocidal polymers derived from lithocholic acid

Mitra S Ganewatta  1   2 , Md Anisur Rahman  1 , Louis Mercado  1 , Tinom Shokfai  3 , Alan W Decho  3 , Theresa M Reineke  2 , Chuanbing Tang  1
Affiliations

Facially amphiphilic polyionene biocidal polymers derived from lithocholic acid

Mitra S Ganewatta et al. Bioact Mater. .

Abstract

Bacterial infections have become a global issue that requires urgent attention, particularly regarding to emergence of multidrug resistant bacteria. We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain. Interestingly, by choosing appropriate monomers, these cationic polymers can form core-shell micelles. These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species. It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities. Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers.

Keywords: Antimicrobial polymers; Bile acid; Facial amphiphilicity; Lithocholic acid; Polyionene; Quaternary ammonium.

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Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
(A) Facial amphiphilic structure of lithocholic acid; and (B) the functional importance of this structure in antimicrobial polymers for conferring destructive membrane interactions promoting antimicrobial activity.
Fig. 2
Fig. 2
(A) Synthesis of main-chain cationic polymers from lithocholic acid. Polymer labels denoted as Pm,n. where m is the number of methylene groups in the dibromide linker and n is the number of methylene groups in the ditertiary amine linker; (B) The structure of Pcontrol that was synthesized using 1,12-dodecanediol instead of the lithocholic diol.
Fig. 3
Fig. 3
1H NMR spectra of lithocholic diol, dibromide monomer (in CDCl3), and polymer P5,6 (in DMSO‑d6) from each step of the synthesis.
Fig. 4
Fig. 4
Polymer particle characterization: (A) An image of polymer P5,6 solution in DI water (right) and DI water (left) against a laser; (B) SEM image of the polymer P5,6 micelles; (C) An illustration of polymer micelles where the hydrophobic core is made of the steroidal units and the cationic groups produce the hydrophilic outer layer.
Fig. 5
Fig. 5
Change of pyrene intensity ratio (I3/I1) versus the concentration of polymers in aqueous solution.
Fig. 6
Fig. 6
(A) Antimicrobial activities of polymers as demonstrated by disk diffusion assays; (B) Cumulative release profiles of the antibiotic ampicillin using micelles of P5,6-Ampicillin.
Fig. 7
Fig. 7
Cell viability assay of various polymers against HeLa cells.
See this image and copyright information in PMC

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