Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases

C. dric 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

doi:https://doi.org/10.3390/md17120699

Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases

C. dric 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

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

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.

Original language	English
Article number	699
Journal	Marine Drugs
Volume	17
Issue number	12
DOIs	https://doi.org/10.3390/md17120699
Publication status	Published - 2019

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Chauvierre, C. D., 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. (2019). Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases. Marine Drugs, 17(12), Article 699. https://doi.org/10.3390/md17120699

@article{5577bec675224f4280814297580c596d,

title = "Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases",

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.",

author = "Chauvierre, {C. dric} and Rachida Aid-Launais and Jo{\"e}l Aerts and Fr{\'e}d{\'e}ric Chaubet and Murielle Maire and Lucas Chollet and Lydia Rolland and Roberta Bonaf{\'e} and Silvia Rossi and Simona Bussi and Claudia Cabella and Laszlo D{\'e}zsi and Tamas F{\"u}l{\"o}p and Janos Szebeni and Youssef Chahid and Zheng, {Kang H.} and Stroes, {Erik S. G.} and {le Guludec}, Dominique and Fran{\c c}ois Rouzet and Didier Letourneur",

year = "2019",

doi = "https://doi.org/10.3390/md17120699",

language = "English",

volume = "17",

journal = "Marine Drugs",

issn = "1660-3397",

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Chauvierre, CD, 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, KH, Stroes, ESG, le Guludec, D, Rouzet, F & Letourneur, D 2019, 'Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases', Marine Drugs, vol. 17, no. 12, 699. https://doi.org/10.3390/md17120699

TY - JOUR

T1 - Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases

AU - Chauvierre, C. dric

AU - Aid-Launais, Rachida

AU - Aerts, Joël

AU - Chaubet, Frédéric

AU - Maire, Murielle

AU - Chollet, Lucas

AU - Rolland, Lydia

AU - Bonafé, Roberta

AU - Rossi, Silvia

AU - Bussi, Simona

AU - Cabella, Claudia

AU - Dézsi, Laszlo

AU - Fülöp, Tamas

AU - Szebeni, Janos

AU - Chahid, Youssef

AU - Zheng, Kang H.

AU - Stroes, Erik S. G.

AU - le Guludec, Dominique

AU - Rouzet, François

AU - Letourneur, Didier

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85076275397&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31842319

U2 - https://doi.org/10.3390/md17120699

DO - https://doi.org/10.3390/md17120699

M3 - Article

C2 - 31842319

SN - 1660-3397

VL - 17

JO - Marine Drugs

JF - Marine Drugs

IS - 12

M1 - 699

ER -

Pharmaceutical development and safety evaluation of a GMP-grade fucoidan for molecular diagnosis of cardiovascular diseases

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