Drug Delivery from PCL/Chitosan Multilayer Coatings for Metallic Implants

This work was partially funded by the FEDER funds through the COMPETE 2020 Program and National Funds through the FCT – Portuguese Foundation for Science and Technology under the projects UIDB/50025/2020-2023 (CENIMAT/I3N), and also partially supported by the project ERC-CoG-2014. The authors would like to thank the use of the traction machine at the Biomaterials Laboratory from the Soft and Bio-functional Materials Group (CENIMAT/I3N).Implant-related infections, mainly caused by Staphylococcus aureus, are a major health concern. Treatment is challenging due to multi-resistant strains and the ability of S. aureus to adhere and form biofilms on bone and implant surfaces. The present work involved the preparation and evaluation of a novel dual polymeric film coating on stainless steel. Chitosan and polycaprolactone (PCL) multilayers, loaded with poly(methyl methacrylate) (PMMA) microspheres encapsulating vancomycin or daptomycin, produced by the dip-coating technique, allowed local antibiotic-controlled delivery for the treatment of implant-related infections. Enhanced adhesion of the film to the metal substrate surface was achieved by mechanical abrasion of its surface. Studies have shown that for both drugs the release occurs by diffusion, but the release profile depends on the type of drug (daptomycin or vancomycin), the pH of the solution, and whether the drug is freestanding (directly incorporated into the films) or encapsulated in PMMA microspheres. Daptomycin freestanding films reached 90% release after 1 day at pH 7.4 and 4 days at pH 5.5. In comparison, films with daptomycin encapsulated microspheres reached 90% release after 2 h at pH 5.5 and 2 days at pH 7.4. Vancomycin encapsulated and freestanding films showed a similar behavior reaching 90% release after 20 h of release at pH 5.5 and 2 and 3 days, respectively, at pH 7.4. Furthermore, daptomycin-loaded films showed activity (assessed by agar diffusion assays) against sensitive (ATCC 25923) and clinically isolated (MRSA) S. aureus strains.publishersversionpublishe