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

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%.

Marine Polysaccharides in Pharmaceutical Applications: Fucoidan and Chitosan as Key Players in the Drug Delivery Match Field

“…However, the pH-responsive profile of fucoidan-chitosan nanoparticles prevents degradation under acidic conditions of the gastrointestinal tract and allows drug absorption in the intestine. Hence, fucoidan-chitosan nanoparticles have been widely explored for oral delivery of active pharmaceutical ingredients [110,111,113,118,[123][124][125][126][127][128][129], also taking advantage of chitosan's property of increased contact with the mucus layer and consequently longer resistance times at the absorption site [129]. The biological properties of fucoidan described in Section 3.1.1 were explored by some authors to obtain synergic effects with a drug, for example, ciprofloxacin [117] or gemcitabine [126].…”

“…Considering fucoidan anticoagulant activity, Silva and collaborators have explored a fucoidan-based nanosystem for oral administration with an antithrombotic effect [125]. To confer higher gastric pH resistance to nanoparticles, the strategy employed glutaraldehyde crosslinks between chitosan chains.…”

Biomaterials from the sea: Future building blocks for biomedical applications

“…Chitosan-fucoidan nanoparticles possess better in vitro anticoagulant activity than pristine fucoidan. Solid evidences showed that this hybrid nanoparticles could reduce thrombus formation even in a deep vein thrombosis model [ 392 ]. The positive surface charge present in chitosan-fucoidan nanoparticles contributes to the increase in activated partial thromboplastin time and is concentration dependent.…”

Marine Polysaccharides as a Versatile Biomass for the Construction of Nano Drug Delivery Systems

“…The vicinal glycols in some marine polysaccharides can be specifically oxidized cleavage by periodate to form aldehyde groups that could subsequently react with amine groups. The Schiff-base reaction is the most commonly used method for preparing CS-based NPs [ 67 , 68 ]. Molecules with more than two active groups may be used as crosslinking agents.…”