Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4

Evaluation of bioactivity of fucoidan from laminaria with in vitro human cell cultures (THP-1)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground: Seaweeds represent one of the few remaining food sources available globally which are not being fully utilized or even over utilized. Kelps (Laminaria spp.) are one of the numerous species of brown seaweeds, a popular marine vegetable, which has been used as a source of iodine and minerals for centuries. Kelps contain anionic polysaccharides called fucoidans heteroglycans with L-fucose units. Their monosaccharide composition, physicochemical and bioactive properties vary between seaweed species. The objective of this work was to evaluate the bioactive properties of laminaria fucoidan (L. digitata and L. hyperborea) toward THP-1 macrophages, a human macrophage like cell line, and investigate its potential antioxidant and immunomodulatory characteristics. Methods: THP-1 macrophages were incubated with five fucoidan concentrations. The Oxygen Radical Absorbance Capacity (ORAC) assay was determined for cell lysates and for the fucoidan extract, in addition to Total Polyphenol Content (TPC). Cytotoxicity of fucoidan was assessed by light microscopy, followed by XTT proliferation assay. Enzyme-linked immunosorbant assays (ELISA) were performed to determine concentrations of the secreted tumor necrosis factor a (TNF-a), interleukin 6 (IL-6), and interleukin 10 (IL-10). Results: Fucoidan did not affect macrophage ability to scavenge oxygen radicals (ORAC) confirming its antioxidant properties toward activated macrophages. The laminaria fucoidan extract at 100 mu g/ml concentration lowered macrophage viability. Lower concentrations of laminaria fucoidan did not have impact on cell viability. Very low concentration of fucoidan at 0.1 mu g/ml triggered secretion of TNF-alpha. However, IL-6 and interleukin IL-10 were expressed when concentration of applied fucoidan was 10 mu g/ml indicating bioactivity of laminaria fucoidan through immunomodulatory actions. Conclusions: The study demonstrated how laminaria fucoidan may have bioactive properties towards THP-1 macrophages. Changes in cytokine secretion between pro-inflammatory (TNF-alpha, and IL-6) and anti-inflammatory (IL-10) cytokines confirmed bioactivity of the laminaria fucoidan extracts.University of Iceland Research Fun

Evaluation of bioactivity of fucoidan from laminaria with in vitro human cell cultures (THP-1)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground: Seaweeds represent one of the few remaining food sources available globally which are not being fully utilized or even over utilized. Kelps (Laminaria spp.) are one of the numerous species of brown seaweeds, a popular marine vegetable, which has been used as a source of iodine and minerals for centuries. Kelps contain anionic polysaccharides called fucoidans heteroglycans with L-fucose units. Their monosaccharide composition, physicochemical and bioactive properties vary between seaweed species. The objective of this work was to evaluate the bioactive properties of laminaria fucoidan (L. digitata and L. hyperborea) toward THP-1 macrophages, a human macrophage like cell line, and investigate its potential antioxidant and immunomodulatory characteristics. Methods: THP-1 macrophages were incubated with five fucoidan concentrations. The Oxygen Radical Absorbance Capacity (ORAC) assay was determined for cell lysates and for the fucoidan extract, in addition to Total Polyphenol Content (TPC). Cytotoxicity of fucoidan was assessed by light microscopy, followed by XTT proliferation assay. Enzyme-linked immunosorbant assays (ELISA) were performed to determine concentrations of the secreted tumor necrosis factor a (TNF-a), interleukin 6 (IL-6), and interleukin 10 (IL-10). Results: Fucoidan did not affect macrophage ability to scavenge oxygen radicals (ORAC) confirming its antioxidant properties toward activated macrophages. The laminaria fucoidan extract at 100 mu g/ml concentration lowered macrophage viability. Lower concentrations of laminaria fucoidan did not have impact on cell viability. Very low concentration of fucoidan at 0.1 mu g/ml triggered secretion of TNF-alpha. However, IL-6 and interleukin IL-10 were expressed when concentration of applied fucoidan was 10 mu g/ml indicating bioactivity of laminaria fucoidan through immunomodulatory actions. Conclusions: The study demonstrated how laminaria fucoidan may have bioactive properties towards THP-1 macrophages. Changes in cytokine secretion between pro-inflammatory (TNF-alpha, and IL-6) and anti-inflammatory (IL-10) cytokines confirmed bioactivity of the laminaria fucoidan extracts.University of Iceland Research Fun