Everolimus immobilisation using polydopamine intermediate layer on poly(l-lactic acid)/poly(d-lactic acid) scaffold for sustainable anti-proliferative drug release

Abstract

Drug-eluting stent (DES) is a widely used treatment to treat atherosclerosis with the incorporation of drugs within/coated on stents. Everolimus is one of the utilised anti-proliferative drugs in developing commercialised DES. However, long-term implantation of DES has contributed to late-stent thrombosis due to rapid release of drug. Therefore, a method such as chemical cross-linking intermediate layer should be adopted in the coating development to sustain the release of drugs. In this work, everolimus was immobilised on polymeric scaffolds of poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) using a polydopamine (PDA) intermediate layer for possible application in DES development. PDA is known for its stability of cross-linking bonds which is beneficial to sustain drug release. In this study, the PLLA/PDLA scaffolds were grafted with the PDA intermediate layer and immobilised with different everolimus concentrations (0.01, 0.05 and 0.10 mM). The ability of PDA to covalently immobilise everolimus was demonstrated through ATR-FTIR, XPS, SEM, AFM, wettability and everolimus quantification. While the sustain release of everolimus was verified through the analyses of drug release and coating stability. The everolimus was successfully immobilised on the PDA layer through O–N and C–O covalent linkages. The flowery-structured everolimus was observed with lower wettability and higher roughness on the greater concentration of everolimus. A sustainable drug release profile was acquired following the zero-order release profile for the 0.05 mM and 0.10 mM everolimus concentrations. The higher everolimus concentration produced greater contribution on the coating stability. These results indicate the capability of PDA to mediate the everolimus immobilisation for sustainable drug release, which is a potential approach in resolving the complication of current DES.