Binary graft modification of polypropylene for anti-inflammatory drug-device combo products

Temperature- and pH-responsive copolymers were γ-ray grafted onto polypropylene (PP) to provide its surface with capability to load and to control the release of nonsteroidal anti-inflammatory drugs (NSAIDs) with the aim of being useful as component of drug-eluting medical devices. Poly(N,N'-dimethylaminoethylmethacrylate) (PDMAEMA) or poly(4-vinylpyridine) (P4VP) were grafted onto PP films via a direct method, and then poly(N-isopropylacrylamide) (PNIPAAm) was grafted applying a preirradiation method. The binary graft copolymers showed hemocompatibility and certain capability to adsorb albumin. (PP-g-DMAEMA)-g-NIPAAm exhibited higher affinity for ibuprofen and, particularly, diclofenac than (PP-g-4VP)-g-NIPAAm. Sustained release was observed under physiological conditions. Cytotoxicity and anti-inflammatory activity of NSAID-eluting (PP-g-DMAEMA)-g-NIPAAm films were evaluated on RAW 264.7 macrophage cells. First, dose dependence of anti-inflammatory activity and cytotoxicity of ibuprofen and diclofenac on RAW 264.7 cells were investigated to elucidate the ranges of drug concentration that the graft copolymers should provide. Optimal concentrations of diclofenac and ibuprofen at which they reduce inflammation while maintaining cell viability were determined to be 200 μg/mL and above 400 μg/mL in culture medium. Sequential grafting of DMAEMA and NIPAAm made PP surface to exhibit remarkably high affinity to diclofenac, being able to load and to regulate drug release fulfilling in vitro requirements to avoid inflammatory response.