Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems
Despite the establishment of systematic antibiotic protections, surgical site infections (SSI) still cause complications after surgery. The reported rates for SSI are usually 2-5%, and sometimes this rate is even higher.
The presence of foreign materials increases the risk of infection. For this reason, pathogens originating from the skin flora can easily penetrate the tissue with the help of capillarity After binding to the suture surfaces, proliferation of pathogens and biofilm formation therein make treatment difficult. Anti-bacterial sutures can be used to prevent this process.
In vitro studies using triclosan for anti-bacterial sutures have shown that triclosan is highly effective in defending against various bacterial pathogens. It also proved a low infection rate in in vivo studies. However, the main disadvantage of using triclosan is that its use is for cosmetic, hygiene and household products. The first research groups reported triclosan resistant bacteria and potential partial selection warnings. Thus, new alternatives were searched and chlorhexidine was selected for antimicrobial preparation of the surgical suture. This antiseptic is highly effective against broad spectrum and clinically dangerous bacteria such as Staphylococcus aureus. The known spectrum of chlorhexidine has been proven in various medical applications such as antiseptic use for mouth and skin and coating of medical devices.
It has been tested whether it is feasible to use slow release carrier systems, which is a new technology to increase antibacterial efficacy. Fatty acids form a lubricating film and reduce the effects of sutures on unwanted sewing. The low solubility of such drug release systems in aqueous media allows the slow release of fatty acid carriers. Palmitic and lauric acid have been chosen as fatty acids.
Various types of coatings have been developed in different concentrations based on chlorhexidine with lauric and palmitic acid in the process of durable dip coating. Cytotoxicity tests were performed using the tensile strengths of the coated sutures, drug releases, antimicrobial effects against S. aureus, and WST 1 assay.
The tensile strength of coated PGA sutures was only influenced by negligible extent in the ethanol-based immersion coating process. All coated sutures undergoing this process showed much higher maximum strength values than required by the Pharmaceutical Europe Standards. It has a much higher strength than the standard. This means that the resistance values of the new coated sutures can be compared to commercial sutures. As a result, no delamination is expected when pulling the sutures from the tissue.
Released drug concentration in PBS for chlorhexidine coated sutures showed a continuous drug release for 96 hours with initial rapid release slowing down significantly after 7 hours. In general, drug release should be as slow as possible, but for long-term protection of coated biomaterial, the antimicrobial effect must be long enough to prevent pathogenesis. The drug release depends on the drug concentration in the coating. The drug carriers mentioned showed a slower drug release, showing a similar microbial effect to the palmitic acid coating lauric acid coating. Moreover, chlorhexidine is released in less than palmitic acid coating. Therefore, sutures coated with a palmitic acid carrier should have a longer in vivo protection potential than the coating using a lauric acid carrier.
The newly coated sutures showed a high antimicrobial effect in agar diffusion tests against S. aureus. Coated sutures formed more than 24 hours of inhibition zones and showed excess activity over several days. The release of chlorhexidine, determined by the inhibition regions, is faster in the first days compared to triclosan because the solubility is higher in aqueous media compared to PBS or agar. This rapid consumption of the materials in the sutures causes premature leaching of inhibition zones. On the other hand, this situation may be useful to prevent early tissue infection. The long-term effects of chlorhexidine-coated sutures against S. aureus lasted up to 5 days at high levels. With regard to drug concentrations, the extent of inhibition zones over time is not very different.
Coated sutures also showed acceptable cytotoxicity at 11 mg / cm , independently of the use of fatty acids in the lowest drug concentration. According to ISO 10993-5: 2009, such sutures should fulfill the non-cytotoxicity required for at least 70% of the persistent metabolic activity of L-929 cells. Thus, 11 μg / ml chlorhexidine-coated sutures are potentially useful for future clinical and human in vivo studies.
In general, it is defined that the antimicrobial-coated suture is strongly associated with the cytotoxicity of the active conjugate attached. The ability to improve biocompatibility with promising drug concentrations without sacrificing high antimicrobial activity seems promising.