Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study

Abstract

Background Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment. Questions/purposes In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels. Methods To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n = 1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n = 3) and the drug release profile from a chitosan sponge device (n = 5). Results With an FIC index \ 0.5, the combination of CHX + VAN exhibited synergism against S aureus. CHX concentrations C 3.91 lg/mL resulted in fibroblast viability decrease, whereas the combination of CHX + VAN did not decrease fibroblast viability until their concentrations reached C 7.81 lg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5. Conclusions CHX + VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth. Clinical Relevance The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.

Chitosan–tripolyphosphate nanoparticles as Arrabidaea chica standardized extract carrier: synthesis, characterization, biocompatibility, and antiulcerogenic activity

“…43 Noel et al 44 and Smith et al 45 suggested the possibility of using a CS sponge device as an alternative to deliver antibiotics locally as an adjunctive therapy for the treatment and prevention of infections, from open traumatic wounds to prophylactic use in surgical sites. Furthermore, a CS sponge can be used as a drug reservoir 43 or a storage form for CS systems.…”

Effects of sodium acetate buffer on chitosan sponge properties andin vivodegradation in a rat intramuscular model

“…15,18,19 Chitopharm S chitosan was purchased from Chitinor AS (Tromsoe, Norway) with 82.5 6 1.7 degree of deacetylation (DDA), 251 6 17 kDa weight-average molecular weight (MW) and 2.013 6 0.145 polydispersity index. All acids and buffer solutions were obtained from Fisher Scientific (Pittsburg, PA).…”

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm

“…Localized antimicrobial drug delivery systems, including biomaterial carrier matrices and coatings on implants, have become a focus to combat biofilm formation and infection for both preventive and treatment strategies [1,7,13,27,29,43,49,63,64]. We provide the initial description of a novel lipid-based material we have developed to serve as a carrier matrix for antibiotics that can be applied to an implant with clinician-selected antibiotics at the point of care.…”

“…The primary strategy for prevention is aseptic surgical technique followed by prophylactic systemic administration of antibiotics [28,71]. Antiinfective biomaterials are increasingly used as an adjunctive strategy to prevent implanted biomaterial infections and to inhibit biofilm-forming microorganisms [13,27,44,49,55,63,64]. Commonly used local antibiotic delivery systems range from antibiotic-loaded bone cement to calcium-based drug delivery systems to sprinkling antibiotics within the wound site [8,24,40,42].…”