Synergistic Co‐Delivery of Membrane‐Disrupting Polymers with Commercial Antibiotics against Highly Opportunistic Bacteria

Abstract

A series of vitamin E-containing biodegradable antimicrobial cationic polycarbonates is designed and synthesized via controlled organocatalytic ring-opening polymerization. The incorporation of vitamin E significantly enhances antimicrobial activity. These polymers demonstrate broad-spectrum antimicrobial activity against various microbes, e.g., S. aureus (Gram-positive), E-coli (Gram-negative) and C. albicans (fungi). More importantly, the co-delivery of such polymers with selected antibiotics (e.g., doxycycline) shows high synergism towards difficult-to-kill bacteria P. aeruginosa. These findings suggest that these vitamin E-functionalized polycarbonates are potentially useful antimicrobial agents against challenging bacterial/fungal infections.

Antimicrobial hydrogels: promising materials for medical application

“…A plethora of antimicrobial synthetic cationic polymers have been reported, including poly(acrylate) and poly(norbornene) systems, poly(arylamide)s poly-β-lactams and polycarbonates. [255][256][257][258][259][260][261][262] Jiang and Cao 263,264 are the frontrunners in this area and have published several works and reviews on zwitterionic polymers such as poly(carboxybetaine) (pCB) and poly(sulfobetaine) (pSB) in the construction of antimicrobial hydrogels. Mi and Jiang 265 reported a new antimicrobial and non-fouling zwitterionic hydrogel through using the antibacterial salicylate International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 44.224.250.200 on 09-Jul-2020 For personal use only.…”

Poly(trimethylene carbonate)-based polymers engineered for biodegradable functional biomaterials

“…Although no report has been published yet, some of the serinol-derived PTMC derivatives ( Figure 3E, F) can be potentially used as polymeric antimicrobials through quaternization and acidolysis of tert-butoxycarbonyl(Boc)-protected side chain affording ammonium salts. 72 Please do not adjust margins Please do not adjust margins Besides the modulation of the primary architecture of the cationic moiety, the introduction of biocompatible biomolecules, 216,218 supramolecular approach, 219 and hydrogelation 220 have also been surveyed to increase and broaden the antimicrobial properties with a low level of hemolytic properties ( Figure 10). In particular, the supramolecular approach raised the importance of the shape of antimicrobials upon the efficacy against some fungi.…”

Helical antimicrobial polypeptides with radial amphiphilicity

“…Because PHLG-BIm can cause membrane disruption and permeabilization, we explored its potential to enhance the antibacterial effect of traditional antibiotics. Synergistic-like enhancement of bacteria killing has been previously reported from coadministration of membrane-disruptive agents with commercial antibiotics (41,55). We selected four antibiotics: streptomycin (aminoglycoside), doxycycline (tetracycline), rifampicin (rifamycin), and gentamicin (aminoglycoside).…”

“…There has also been growing interest in synthetic polymer-based AMP mimics bearing both cationic and hydrophobic groups, which can be prepared through cost-effective polymerization processes. For example, simplified polymeric AMP analogs have been developed, including poly (methacrylamides) (31), poly(β-lactams) (14,(32)(33)(34)(35), polypeptides (36)(37)(38), poly(norborenes) (39,40), and poly(carbonates) (41,42). These compounds are considerably less expensive than peptides, and much work is being done to optimize them.…”