What's new in NSAID pharmacotherapy: oral agents to injectables.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) represent a critically important class of medications useful in numerous musculoskeletal and inflammatory diseases. The focus of NSAID use has recently centered on gastrointestinal (GI) side effects and potential cardiovascular toxicity. Innovative new oral and intra-articular pharmaceutically engineered dosage forms are examined. We review recently developed intravenous NSAIDs and their potential advantages over oral products in the perioperative setting. DESIGN: Databases searched included PubMed, Google Scholar, Ovid, and Athens. We contacted key U.S. and Japanese manufactures who are developing new and innovative NSAID technologies for inclusion in this overview. Early attempts at mitigating GI toxicity with oral agents combined with gastroprotective additives are outlined. RESULTS: Contemporary technologies coupled with uniquely advanced pharmaceutical manipulations to improve safety and efficacy are discussed including combined vasodilating agent naproxcinod as the prototypical cyclooxygenase-inhibiting nitric oxide (NO) donor; hydrogen sulfide-releasing compounds to protect GI mucosa; glycoscience technologies combining the intra-articular hyaluronic acid SI-613 combined with NSAIDs; and nano-formulated SoluMatrix submicron technologies that include diclofenac, indomethacin, naproxen, and meloxicam. CONCLUSIONS: New NSAIDs under development are intended to address GI and cardiovascular pitfalls inherent to current therapy options across the entire NSAID drug class. NO or hydrogen sulfide donating drugs, new reliable injectables for perioperative and inpatient use, novel intra-articular extended-release NSAIDs combined with IAHA, and nano-formulations of submicron NSAIDs featuring delivery of decreased doses without diminished efficacy promise to afford innovative technologies that likely will be the future of NSAID therapy.

Endotoxin binding by sevelamer: potential impact on nutritional status.

Patients on hemodialysis (HD) have a high burden of chronic inflammation induced associated with multiple comorbidities including poor nutritional status. Endotoxin (ET) is a Gram-negative bacterial cell wall component and a potent stimulus for innate immune system activation leading to the transcription of proinflammatory cytokines (e.g., IL-1, IL-6, and TNFα) that adversely affect protein metabolism and nutrition. Several cross-sectional observational studies have found that elevated serum ET concentrations in hemodialysis patients are associated with lower serum albumin, higher proinflammatory cytokine, and C-reactive protein concentrations. Possible sources of ET in the systemic circulation are bacterial translocation from the gastrointestinal tract and iron supplementation, potentially leading to intestinal bacterial overgrowth. Sevelamer is a nonabsorbable hydrogel approved for use as a phosphate binder in HD patients. Reductions in serum ET concentrations in hemodialysis patients have been observed with sevelamer therapy in observational studies and the few published interventional studies. Reduction of ET concentrations was associated with concomitant reductions in TNFα, IL-6, and CRP and improvement in serum albumin in the majority of these small studies. Additional studies are needed to evaluate the potential effects of sevelamer treatment on nutritional status in chronic kidney disease (CKD) patients with elevated ET.

Synthesis of gold and silver nanoparticles stabilized with glycosaminoglycans having distinctive biological activities.

Metal nanoparticles have been studied for their anticoagulant and anti-inflammatory efficacy in various models. Specifically, gold and silver nanoparticles exhibit properties that make these ideal candidates for biological applications. The typical synthesis of gold and silver nanoparticles incorporates contaminants that could pose further problems. Here we demonstrate a clean method of synthesizing gold and silver nanoparticles that exhibit biological functions. These nanoparticles were prepared by reducing AuCl(4) and AgNO(3) using heparin and hyaluronan as both reducing and stabilizing agents. The particles show stability under physiological conditions and narrow size distributions for heparin particles and wider distribution for hyaluronan particles. Studies show that the heparin nanoparticles exhibit anticoagulant properties. Additionally, either gold- or silver-heparin nanoparticles exhibit local anti-inflammatory properties without any significant effect on systemic hemostasis upon administration in carrageenan-induced paw edema models. In conclusion, gold and silver nanoparticles complexed with heparin demonstrated effective anticoagulant and anti-inflammatory efficacy, having potential in various local applications.