Original ArticleInduction of Nicotinamide–Adenine Dinucleotide Phosphate Oxidase and Apoptosis by Biodegradable Polymers in Macrophages: Implications for StentsPotnis, Pushya A PhD, MPH*; Tesfamariam, Belay PhD†; Wood, Steven C PhD*Author Information From the *Division of Biology, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health (CDRH); and †Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD. Received for publication January 13, 2011; accepted March 14, 2011. Supported by funds provided by the Office of Science and Engineering Laboratories and the Food and Drug Administration. The opinions expressed in this article are those of the authors and do not represent the FDA policy. The authors declare no conflicts of interest. Reprints: Pushya A. Potnis, Office of Engineering and Science Laboratory, CDRH, FDA, Building 64, Rm 3022, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002 (e-mail: email@example.com). Journal of Cardiovascular Pharmacology: June 2011 - Volume 57 - Issue 6 - p 712-720 doi: 10.1097/FJC.0b013e31821a4f1e Buy Metrics Abstract The drug-eluting stent platform has a limited surface area, and a polymer carrier matrix is coated to enable sufficient loading of drugs. The development of a suitable polymer has been challenging because it must exhibit biocompatibility with the intravascular milieu. The use of biodegradable polymers seems to be attractive because it enables drug release as it degrades and is eventually eliminated from the body leaving the permanent metallic stent polymer-free. The aim of this study was to investigate the biocompatibility of biodegradable polymers using the human monocyte cell line. Cultured monocytes differentiated into functional macrophages (THP-1) were incubated with various polymers including poly-l-lactide (PLA), polycaprolactone (PCL), or poly-d, l-lactide-co-glycolide (PLGA) for up to 5 days. Exposure of cells to the polymers resulted in macrophage-polymer adhesion and induced marked pro-oxidant species as measured by calcein AM uptake assay and flow cytometric analysis of 2′,7′-dichlorofluorescin fluorescence, respectively. Real-time reverse-transcription polymerase chain reaction and Western blot analysis of expression of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases revealed enhanced expression of NADPH oxidase subunits in response to PLA and PLGA compared with that of PCL. Flow cytometric analysis of fluorescein isothiocyanate-Annexin V and propium iodide-stained PLA and PGLA polymer-exposed THP-1 cells showed early and late apoptotic changes. Similarly, exposure to the PLA and PGLA polymers, but not to the PCL polymer, resulted in enhanced staining for cleaved poly(ADP-ribose) polymerase-1, a protein fragment produced by caspase cleavage. These results indicate that biodegradable polymers are associated with cell adhesion, NADPH oxidase-induced generation of reactive oxygen species and excess apoptosis. © 2011 Lippincott Williams & Wilkins, Inc.