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      A promising oral fucoidan-based antithrombotic nanosystem: Development, activity and safety.

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          Abstract

          Fucoidan-loaded nanoparticles emerge as great candidates to oral anticoagulant therapy, due to increasing of bioavailability and circulation time of this natural anticoagulant. Crosslink between chitosan chains are performed using glutaraldehyde to confer higher gastric pH resistance to nanoparticle matrices. In this work, chitosan-fucoidan nanoparticles, without (NpCF) and with glutaraldehyde crosslink (NpCF 1% and NpCF 2%), were prepared to evaluate their anticoagulant, antithrombotic and hemorrhagic profile. Nanoparticles were characterized by average diameter, polydispersity index, zeta potential, Fourier transform infrared spectroscopy and fucoidan in vitro release. Anticoagulant and antithrombotic activities were determined by in vitro and in vivo models, respectively. Hemorrhagic profile was in vivo evaluated by tail bleeding assay. Preparations showed nanometric and homogeneous average diameters. Zeta potentials of NpCF and NpCF 1% were stable over gastrointestinal pH range, which was confirmed by low fucoidan release in gastric and enteric media. In pH 7.4, NpCF and NpCF 1% demonstrated fucoidan release of 65.5% and 60.6%, respectively, within the first 24 hours. In comparison to fucoidan, NpCF and NpCF 1% showed increased in vitro anticoagulant activity. A significant difference on oral antithrombotic profile of NpCF 1% was found in comparison to fucoidan. Bleeding profile of NpCF and NpCF 1% showed no differences to control group, indicating the safety of these systems. Surprisingly, oral antithrombotic profile of commercially available fucoidan, from Fucus vesiculosus, has not been previously determined, which reveals new possibilities. In this work, significant advances were observed in anticoagulant and antithrombotic profiles of fucoidan through the preparation of NpCF 1%.

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          Author and article information

          Journal
          Nanotechnology
          Nanotechnology
          IOP Publishing
          1361-6528
          0957-4484
          Feb 09 2018
          Affiliations
          [1 ] Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de JAneiro, RJ, BRAZIL.
          [2 ] Trinity College Dublin School of Pharmacy and Pharmaceutical Sciences, Dublin, IRELAND.
          Article
          10.1088/1361-6528/aaae5b
          29424698
          f02357e3-d9d2-4ce6-a7f5-6d2ed80311f4
          © 2018 IOP Publishing Ltd.

          anticoagulants,antithrombotic agents,chitosan,fucoidan,nanoparticles

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