Abstract
We investigated poly(L-lactic acid) (PLLA) fibers and coils, simulating stents and the influence of impregnation with curcumin, a non-steroidal anti-inflammatory drug, intended to reduce the pro-inflammatory property of these implants. Fibers obtained by melt extrusion of 137 kDa PLLA resin containing 10% curcumin (C-PLLA) exhibited a stable curcumin release rate for periods up to 36 days. Curcumin increased the fiber tensile strength at break and decreased embrittlement vs . controls in 36 day 37°C saline incubation. A mouse peritoneal phagocyte model was employed to test the anti-inflammatory properties of C-PLLA fibers in vitro. Myeloperoxidase and non-specific esterase activity assays were performed for adherent cells (polymorphonuclear leukocytes (PMN) and macrophages (MΦ), respectively). PMN and MΦ adhesion to C-PLLA fibers were significantly reduced compared to control PLLA fibers (2.6 ± 0.91) × 105 vs. (5.6 ± 0.67) × 105 PMN/cm2 and (3.9 ± 0.23) × 103 vs. (9.1 ± 0.7) × 103 MΦ/cm2 (P < 0.05), respectively. In addition, superoxide release in the phagocyte pool contacting C-PLLA fibers was 97% less than that for PLLA controls. A fresh human whole blood recirculation system was employed to analyze cell adhesion under flow conditions, employing scanning electron microscopy (SEM). Reduced adhesion of cells on C-PLLA fiber coils vs. controls was observed. These in vitro studies demonstrate that bulk curcumin impregnation can reduce the inflammatory response to bioresorbable PLLA fibers, whilst improving mechanical properties, thereby suggesting curcumin loading may benefit PLLA-based implants.
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