期刊
MARINE DRUGS
卷 17, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/md17120699
关键词
GMP-grade fucoidan; regulatory toxicology; molecular diagnosis; scintigraphy
资金
- EU (NanoAthero project) [FP7-NMP-2012-LARGE-6-309820, ANR-13-LAB1-0005-01, ANR-13-RPIB-0006]
- Agence Nationale de la Recherche (ANR) [ANR-13-LAB1-0005, ANR-13-RPIB-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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 mu g/kg (x500 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 Tc-99m-fucoidan as an imaging agent to detect activated endothelium in humans.
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