Characterization of a novel active release coating to prevent biofilm implant‐related infections

Abstract

Biofilm implant-related infections cost the US healthcare system billions of dollars each year. For several decades, device coatings have been developed that actively release antimicrobial compounds in an attempt to prevent these infections from developing. To date, few coatings have been put into clinical use. These have shown limited to no efficacy in clinical trials. Recent data have shown the in vitro and in vivo efficacy of a novel active release coating that may address the limitations of coatings that are used clinically. In this study, the novel active release coating was characterized to gain an understanding of the effects of combining an antimicrobial additive, cationic steroid antimicrobial-13 (CSA-13), to a medical grade polydimethylsiloxane (PDMS) material. Results indicated that the addition of CSA-13 did influence the physical properties of the PDMS, but not with adverse effects to the desired material properties. Furthermore, there was no indication of chemical reactivity. It was shown that CSA-13 was uniformly dispersed as small particles throughout the PDMS matrix. These particles were able to dissolve and elute out of the PDMS within a 30-day period. The results of this work suggested that the PDMS with CSA-13 was thermally, chemically and physically stable when used as a device coating to treat local infection and/or prevent biofilm implant-related infections from developing.

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection

“…Additionally, this low-molecular-mass compound has potent activity against bacterial biofilms (32,33). Some previous studies undertook evaluations of CSA-13 activity using in vitro systems and different experimental settings dedicated to evaluation of activity against resistant strains (31,34), in different body fluids (32), in the presence of different polyelectrolytes (35,36), or using drug release systems and antimicrobial coating (32,37,38). However, only a few studies have evaluated the activity of CSA-13 in cell cultures or animal models (13,39,40).…”

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

“…Williams et al [99] characterized physical and chemical properties of a coating containing CSA-13 as a novel active release agent in a medical grade polymer coating on fracture fixation plates. Studies of polymerization of the silicone coating demonstrated that incorporation of CSA-13 (18% w/w) did not impact the physical properties of the coating.…”

Ceragenins – a new weapon to fight multidrug resistant bacterial infections

“…Recently, antimicrobial nanoparticles were synthesised using ceragenins and they were introduced as multifunctional theranostics [33]. Different applications of ceragenins include contact lenses, hydrogels with an antibacterial innate immune function [34], polymeric coating applied to implanted devices to prevent perioperative device-related infections [35], thermally, chemically, and physically stable medical grade polydimethylsiloxane (PDMS) material to prevent biofilm formation [36], silicon [37], and gene delivery systems [38] (Figure 2). Similarly to cathelicidin-related antimicrobial peptides [15], ceragenins that mimic the hydrophobic and cationic morphology of cathelicidin have antiproliferative effects on the colon cancer-derived cell line HCT116.…”