Back to Search
Start Over
Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases
- Source :
- Marine drugs, Marine drugs, MDPI, 2019, 17 (12), ⟨10.3390/md17120699⟩, Marine Drugs, Volume 17, Issue 12, Marine Drugs, 17(12):699. Multidisciplinary Digital Publishing Institute, Marine drugs, MDPI, 2019, 17 (12), pp.699. ⟨10.3390/md17120699⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
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 &mu<br />g/kg (&times<br />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.
- Subjects :
- Male
regulatory toxicology
MESH: Rats
Swine
[SDV]Life Sciences [q-bio]
Myocardial Reperfusion Injury
Article
MESH: Dose-Response Relationship, Drug
Drug Development
Polysaccharides
molecular diagnosis
Animals
scintigraphy
MESH: Animals
Rats, Wistar
MESH: Swine
ComputingMilieux_MISCELLANEOUS
MESH: Drug Development
Dose-Response Relationship, Drug
MESH: Molecular Weight
GMP-grade fucoidan
scintigraphy, regulatory toxicology, molecular diagnosis, GMP-grade fucoidan
Technetium
MESH: Rats, Wistar
MESH: Male
MESH: Myocardial Reperfusion Injury
Rats
Molecular Weight
Disease Models, Animal
P-Selectin
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
MESH: Polysaccharides
MESH: P-Selectin
MESH: Technetium
Female
Radiopharmaceuticals
MESH: Disease Models, Animal
MESH: Female
MESH: Radiopharmaceuticals
Subjects
Details
- Language :
- English
- ISSN :
- 16603397
- Database :
- OpenAIRE
- Journal :
- Marine drugs, Marine drugs, MDPI, 2019, 17 (12), ⟨10.3390/md17120699⟩, Marine Drugs, Volume 17, Issue 12, Marine Drugs, 17(12):699. Multidisciplinary Digital Publishing Institute, Marine drugs, MDPI, 2019, 17 (12), pp.699. ⟨10.3390/md17120699⟩
- Accession number :
- edsair.pmid.dedup....354abc829d4015ec073c6ca8f77d1ded