Inflammation is the initial response of the immune system to potentially harmful stimuli (e.g., injury, stress, and infections). The process involves activation of macrophages and neutrophils, which produce mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) are considered as biomarkers of inflammation. Even though it occurs as a physiological defense mechanism, its involvement in the pathogenesis of various diseases is reported. Rheumatoid arthritis, inflammatory bowel disease, Alzheimer’s disease, and cardiovascular diseases are only a part of the diseases, in which pathogenesis the chronic inflammation is involved. Fucoidans are complex polysaccharides from brown seaweeds and some marine invertebrates, composed mainly of L-fucose and sulfate ester groups and minor amounts of neutral monosaccharides and uronic acids. Algae-derived fucoidans are studied intensively during the last years regarding their multiple biological activities and possible therapeutic potential. However, the source, species, molecular weight, composition, and structure of the polysaccharides, as well as the route of administration of fucoidans, could be crucial for their effects. Fucoidan is reported to act on different stages of the inflammatory process: (i) blocking of lymphocyte adhesion and invasion, (ii) inhibition of multiple enzymes, and (iii) induction of apoptosis. In this review, we focused on the immunemodulating and anti-inflammatory effects of fucoidans derived from macroalgae and the models used for their evaluation. Additional insights on the molecular structure of the compound are included.

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.

The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release.

Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells-neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60 mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K(+) efflux may be the underlying cause for the effect of retigabine on the muscle tone.

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