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Open AccessArticle

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

1
Université de Paris, UMRS1148, INSERM, F-75018 Paris, France
2
X. Bichat Medical School, Université de Paris, UMS34 FRIM, F-75018 Paris, France
3
AP-HP, Department of Nuclear Medicine, X. Bichat Hospital, F-75018 Paris, France
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Algues & Mer, F-29242 Ouessant, France
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Bracco Research Center, Bracco Imaging Spa, 20811 Colleretto Giacosa, Italy
6
Nanomedicine Research and Education Center, Semmelweis University, 1085 Budapest, Hungary
7
Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(12), 699; https://doi.org/10.3390/md17120699
Received: 15 November 2019 / Revised: 4 December 2019 / Accepted: 9 December 2019 / Published: 12 December 2019
(This article belongs to the Special Issue Vascular Bioactivities of Marine Natural Products)
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. View Full-Text
Keywords: GMP-grade fucoidan; regulatory toxicology; molecular diagnosis; scintigraphy GMP-grade fucoidan; regulatory toxicology; molecular diagnosis; scintigraphy
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Chauvierre, C.; Aid-Launais, R.; Aerts, J.; Chaubet, F.; Maire, M.; Chollet, L.; Rolland, L.; Bonafé, R.; Rossi, S.; Bussi, S.; Cabella, C.; Dézsi, L.; Fülöp, T.; Szebeni, J.; Chahid, Y.; Zheng, K.H.; Stroes, E.S.G.; Le Guludec, D.; Rouzet, F.; Letourneur, D. Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases. Mar. Drugs 2019, 17, 699.

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