Design, development, and validation of chitosan-based coating via catechol oxidation for controlled drug release

Central venous catheters (CVCs) are largely used to administer chemotherapy, hemodialysis, and other treatments. Mostly made of polydimethylsiloxane (PDMS), these medical devices present an intrinsic risk of infection due to the possible formation of biofilm, thus increasing the risk of complications, also known as Central line-associated bloodstream infection (CLABSI). Drug-releasing polymer coatings are a well-recognized strategy for combating biofilm formation. However, the coating's stability on the substrate throughout time is a major challenge. Therefore, this work aims to develop a chitosan-based coating designed to have maximum adhesion and stability to ensure sustained drug release and antibacterial properties over time. A coating composed of chitosan (CS) as a drug carrier, caffeic acid (CA) and copper sulphate (Cu) as crosslinkers, and moxifloxacin (Mox) as an antibiotic, was deposited through a casting and dip-coating process onto functionalized PDMS surface. A crucial factor for the stability of the coating is the environment in which it will be implanted. As far as we know, the study of coating stability under flow (i.e. shear stress) and in the presence of a pseudo-physiological medium that mimics human plasma under such conditions has not yet been addressed in the literature. The results showed that chitosan without the presence of crosslinkers (control formulation) is not able to provide controlled release and prolonged antibacterial activity against E. coli and S. aureus. On the other hand, the optimized formulation was able to demonstrate antibacterial activity for up to 21 days, without demonstrating toxicity to human dermal fibroblasts and showed greater adhesion strength than the control formulation. By comparing the control formulation with the optimized formulation, it was evident that the later had increased stability over time. Thus, these results encourage the application of the technology developed here to produce antibacterial coatings based on chitosan for CVCs made of PDMS to control CLABSI, as well as an original method developed for checking the stability of coatings in vitro, mimicking some of the conditions reported in vivo.