Development of Polymer Microcapsules Functionalized with Fucoidan to Target P‐Selectin Overexpressed in Cardiovascular Diseases

• Published in: Advanced healthcare materials 2017-02, Vol.6 (4), p.np-n/a
• Main Authors: Li, Bo, Juenet, Maya, Aid‐Launais, Rachida, Maire, Murielle, Ollivier, Véronique, Letourneur, Didier, Chauvierre, Cédric
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Aortic Aneurysm, Abdominal - diagnostic imaging; Aortic Aneurysm, Abdominal - metabolism; Assaying; Binding; Capsules; Cardiology and cardiovascular system; Carriers; Disease Models, Animal; Diseases; Drug Delivery Systems - methods; Engineering Sciences; fucoidan; Heart diseases; Human health and pathology; Humans; Imaging; Life Sciences; Male; Medical services; Mice; Micro and nanotechnologies; Microelectronics; Molecular Imaging - methods; molecular targeting; P-Selectin - metabolism; Platelets; polymer microcapsules; Polysaccharides - chemistry; Polysaccharides - pharmacokinetics; Polysaccharides - pharmacology; P‐selectin; Rats; Rats, Wistar; thrombosis; Thrombosis - diagnostic imaging; Thrombosis - metabolism
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201601200

New tools for molecular imaging and targeted therapy for cardiovascular diseases are still required. Herein, biodegradable microcapsules (MCs) made of polycyanoacrylate and polysaccharide and functionalized with fucoidan (Fuco‐MCs) are designed as new carriers to target arterial thrombi overexpressing P‐selectin. Physicochemical characterizations demonstrated that microcapsules have a core–shell structure and that fucoidan is present onto the surface of Fuco‐MCs. Furthermore, their sizes range from 2 to 6 µm and they are stable on storage over 30 d at 4 °C. Flow cytometry experiments evidenced the binding of Fuco‐MCs for human activated platelets as compared to MCs (mean fluorescence intensity: 12 008 vs. 9, p < 0.001) and its absence for nonactivated platelets (432). An in vitro flow adhesion assay showed high specific binding efficiency of Fuco‐MCs to P‐selectin and to activated platelet aggregates under arterial shear stress conditions. Moreover, both types of microcapsules reveal excellent compatibility with 3T3 cells in cytotoxicity assay. One hour after intravenous injection of microcapsules, histological analysis revealed that Fuco‐MCs are localized in the rat abdominal aortic aneurysm thrombotic wall and that the binding in the healthy aorta is low. In conclusion, these microcapsules appear as promising carriers for targeting of tissues characterized by P‐selectin overexpression and for their molecular imaging or treatment. Targeted core–shell polymer microcapsules are developed as potential theranostic microcarriers for thrombosis diseases. The microcapsule surface is functionalized by fucoidan, which gives microcapsules the property of specificity to P‐selectin under blood flow conditions. Meanwhile, organic core is considered to a potential loading space of probe and/or hydrophobic drug for the diagnosis and/or the treatment of vascular diseases overexpressing P‐selectin.