Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases
by
Cédric Chauvierre 1,*
, Rachida Aid-Launais 1,2, Joël Aerts 2,3, Frédéric Chaubet 1, Murielle Maire 1, Lucas Chollet 1,4, Lydia Rolland 4, Roberta Bonafé 5, Silvia Rossi 5, Simona Bussi 5, Claudia Cabella 5, Laszlo Dézsi 6, Tamas Fülöp 6, Janos Szebeni 6, Youssef Chahid 7, Kang H. Zheng 7, Erik S. G. Stroes 7, Dominique Le Guludec 1,2,3, François Rouzet 1,2,3 and Didier Letourneur 1
Cédric Chauvierre 1,*, Rachida Aid-Launais 1,2, Joël Aerts 2,3, Frédéric Chaubet 1, Murielle Maire 1, Lucas Chollet 1,4, Lydia Rolland 4, Roberta Bonafé 5, Silvia Rossi 5, Simona Bussi 5, Claudia Cabella 5, Laszlo Dézsi 6, Tamas Fülöp 6, Janos Szebeni 6, Youssef Chahid 7, Kang H. Zheng 7, Erik S. G. Stroes 7, Dominique Le Guludec 1,2,3, François Rouzet 1,2,3 and Didier Letourneur 1
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
4
Algues & Mer, F-29242 Ouessant, France
5
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.
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MDPI and ACS Style
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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