Assessment of acrylic bone cement as a local delivery vehicle for the application of non-steroidal anti-inflammatory drugs.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to reduce the inflammation and pain in patients suffering from arthritis. There is a possible use for these drugs in the treatment of inflammation associated with periodontitis. However, the propensity of NSAIDs to cause serious side effects, including gastrointestinal bleeding, has reduced their usefulness. The local application of NSAIDs can avoid these side effects by delivering low doses of drug directly to the affected site. Three NSAIDs (indomethacin, tolmetin and mefenamic acid) were incorporated into polymethylmethacrylate bone cement (PM MA) strips in a range of concentrations and their cytotoxicity, pattern of drug release and ability to suppress elevated levels of prostaglandin E2 (PGE2) in cultured human periodontal ligament fibroblasts (HPLF) assessed. The strips released between 10 and 30% of the total incorporated drug over 7 days, with the highest levels released by strips containing 20% w/w of drug. Strips containing 20% indomethacin and mefenamic acid released in excess of toxic levels in the first 24 h. Strips containing 20, 10 and 5% w/w NSAID significantly (P < 0.05) reduced the level of PGE2 expression by E. coli lipopolysaccharide (LPS) challenged cells, with only the 20% mefenamic acid strip performing significantly better than the other drugs. We conclude that local delivery of NSAIDs using PMMA as a sustained release vehicle is a possible additional tool in the treatment of periodontitis.
Division of Restorative Dentistry, Bristol Dental School, UK.
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Corry
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Moran
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D001843:Bone Cements / Q000737:chemistry*; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D015232:Dinoprostone / Q000378:metabolism; D004337:Drug Carriers; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000737:chemistry / Q000627:therapeutic use; D008528:Mefenamic Acid / Q000737:chemistry / Q000627:therapeutic use; D010513:Periodontal Ligament / Q000187:drug effects*; D010518:Periodontitis / Q000188:drug therapy; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D014046:Tolmetin / Q000737:chemistry / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001843:Bone Cements; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008528:Mefenamic Acid; D019904:Polymethyl Methacrylate; D014046:Tolmetin; D015232:Dinoprostone; D007213:Indomethacin