Poly(lactide-co-trimethylene carbonate) coatings with ciprofloxacin, fusidic acid and azithromycin. The effect of the drug on the degradation and biological activity against different Staphylococcus reference strains

Metallic implants are very popular and frequently used. However, the implantation procedure is often associated with accompanying infections. To reduce this problem mono- and multi-drug loaded biodegradable poly(lactide-trimethylene carbonate) P(L/TMC) coatings have been developed. Three antibiotics were chosen for that purpose: azithromycin dihydrate (AZT), fusidic acid (FA) and ciprofloxacin (CFX). Popular titanium alloy, Ti6Al7Nb was used as a metal substrate. Since regular degradation process is very advantageous for medical applications, drug delivery systems were characterized during degradation. The 20% weight loss was detected after 4 weeks and this effect was similar for all samples. NMR analysis indicated stable course of degradation that was characterized by the similar content of the comonomer unit in the polymer chain at every stage of degradation. The addition of ciprofloxacin and fusidic acid molecules caused changes in thermal properties: drug molecules acted as nucleating agents and introduced changes in the crystallinity of the matrices. Changes of thermal properties were also observed during degradation. Endothermic peak corresponding to CFX or FA gradually decreased on DSC curves with the degradation time. Antibacterial activity was confirmed towards Staphylococcus aureus (methicillin sensitive and methicillin resistant) and Staphylococcus epidermidis strains (biofilm-forming and without ability to form biofilm) in the case of P(L/TMC) + CFX, P(L/TMC) + FA. The P(L/TMC) + AZT did not show antibacterial activity towards methicillin resistant Staphylococcus aureus strain and biofilm-forming Staphylococcus epidermidis. Combining ciprofloxacin, fusidic acid and azithromycin into one biodegradable coating did not enhance the antibacterial effect. The drug-free P(L/TMC) coatings did not show the eradication activity, which confirms that the antibacterial effect was caused exclusively by the released drug. Local release of the drug allows to eliminate systemic administration and significantly reduce the drug dose. It might also improve effectiveness of the treatment by the high concentration of the drug at the implantation site. Biodegradable coatings on commonly used metallic implants can be promising solution for prophylaxis of nosocomial infections since they can act as drug delivery systems releasing the antibiotics.