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Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases.

Marine drugs (2019-12-18)
Cédric Chauvierre, Rachida Aid-Launais, Joël Aerts, Frédéric Chaubet, Murielle Maire, Lucas Chollet, Lydia Rolland, Roberta Bonafé, Silvia Rossi, Simona Bussi, Claudia Cabella, Laszlo Dézsi, Tamas Fülöp, Janos Szebeni, Youssef Chahid, Kang H Zheng, Erik S G Stroes, Dominique Le Guludec, François Rouzet, Didier Letourneur
ABSTRACT

The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made of a sulfated fucose-rich polysaccharides (fucoidan) and a radionuclide (technetium-99m) for the detection of P-selectin expression in cardiovascular diseases. After extraction and fractionation from brown seaweeds, the good manufacturing practice (GMP) production of a low molecular weight (LMW) fucoidan of 7 kDa was achieved and full physicochemical characterization was performed. The regulatory toxicology study in rats of the GMP batch of LMW fucoidan revealed no adverse effects up to 400 μg/kg (×500 higher than the expected human dose) and pseudoallergy was not seen as well. In a myocardial ischemia-reperfusion model in rats, the GMP-grade LMW fucoidan labeled with technetium-99m detected P-selectin upregulation in vivo. The present study supports the potential of using 99mTc-fucoidan as an imaging agent to detect activated endothelium in humans.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
L-(−)-Fucose, ≥99%