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Crosslinks 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 profiles. Nanoparticles were characterized by average diameter (AD), polydispersity index, zeta potential, Fourier transform infrared spectroscopy and fucoidan\n                    <jats:italic>in vitro<\/jats:italic>\n                    release. Anticoagulant and antithrombotic activities were determined by\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, respectively. Hemorrhagic profile was\n                    <jats:italic>in vivo<\/jats:italic>\n                    evaluated by tail bleeding assay. Preparations showed nanometric and homogeneous ADs. Zeta potentials of NpCF and NpCF 1% were stable over the 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 h. In comparison to fucoidan, NpCF and NpCF 1% showed increased\n                    <jats:italic>in vitro<\/jats:italic>\n                    anticoagulant activity. A significant difference in the oral antithrombotic profile of NpCF 1% was found in comparison to fucoidan. Bleeding profile of NpCF and NpCF 1% showed no differences to the control group, indicating the safety of these systems. Surprisingly, the oral antithrombotic profile of commercially available fucoidan, from\n                    <jats:italic>Fucus vesiculosus<\/jats:italic>\n                    , has not been previously determined, which reveals new possibilities. In this work, significant advances were observed in the anticoagulant and antithrombotic profiles of fucoidan through the preparation of NpCF 1%.\n                  <\/jats:p>","DOI":"10.1088\/1361-6528\/aaae5b","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T11:46:04Z","timestamp":1518176764000},"page":"165102","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["A promising oral fucoidan-based antithrombotic nanosystem: development, activity and safety"],"prefix":"10.1088","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-5756","authenticated-orcid":false,"given":"L C R P","family":"da Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Todaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F A","family":"do Carmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F S","family":"Frattani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V P","family":"de Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Sathler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Cabral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"nanoaaae5bbib1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1161\/CIRCULATIONAHA.114.008302","type":"journal-article","article-title":"Documenting the global burden of cardiovascular disease: a major achievement but still a work in progress","volume":"129","author":"Yusuf","year":"2014","journal-title":"Circulation"},{"key":"nanoaaae5bbib2","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/jth.12127","type":"journal-article","article-title":"The history and historical treatments of deep vein thrombosis","volume":"11","author":"Galanaud","year":"2013","journal-title":"J. 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