Biovector Therapeutics, S.a.

A Et S Biovecteurs

Jaouad Meniali

Daniel Samain

Li Ding

Pascal E Delrieu

Ignacio De Miguel

Karim Ioualalen

Monique Cervilla

Laurent Imbertie

Valerie Rieumajou

A biodegradable particulate vector for transporting biologically active molecules is prepared containing a nucleus formed of a cross-linked polysaccharide or oligosaccharide matrix having grafted ionic ligands, a layer of fatty acid compounds covalently bonded to the nucleus and a layer of phospholipids hydrophobically bonded to the layer of fatty acid compounds. Dextran, cellulose or starch may be cross-linked with epichlorohydrin to form a cross-linked polysaccharide matrix. Ionic ligands may be grafted using an acidic compound such as succinic acid, phosphoric acid or phosphorous oxychloride, or a basic compound such as choline, hydroxycholine, 2-(dimethylamino)ethanol or 2-(dimethylamino) ethylamine fastened onto the grafted acidic compound. Phosphoric acid or phosphorous oxychloride in one step provide both cross-linking and ionic ligands. Co-cross-linking can be obtained using a protein such as keratin, collagen or elastase. The vector may be prepared by reacting succinic acid monochloride with a cross-linked polysaccharide matrix to graft succinic acid onto the matrix to form the nucleus having ionic ligands, grinding the nucleus to a size between 10 .mu.nm and 10 .mu.m, drying, coupling fatty acid compounds to the nucleus and hydrophobically bonding phospholipids to the fatty acid compounds. After coupling the fatty acid compounds and before bonding the phospholipids, a molecule having biological activity may be added. The succinic acid monochloride is preferably prepared by reacting succinic acid dichloride with free succinic acid to form pure crystalline succinic acid monochloride.

Biodegradable particulate vector for transporting molecules having

A biodegradable particulate vector for transporting biologically active molecules is prepared containing a nucleus for containing a biologically active molecule, a first layer of fatty acid compounds covalently bonded to the nucleus and a second layer of phospholipids hydrophobically bonded to the first layer. The nucleus is between 10 nm and 10 .mu.m in size and is formed of a cross-linked polysaccharide or oligosaccharide matrix onto which ionic ligands are uniformly grafted. The cross-linked polysaccharide may be dextran, cellulose or starch cross-linked with epichlorohydrin. The ligand may be an acidic compound selected from succinic acid, phosphoric acid, citric acid, glycine, alanine, glutamic acid and aspartic acid, or a basic compound such as choline, hydroxycholine, 2-(dimethylamino)ethanol or 2-(dimethylamino)ethylamine fastened onto the matrix via the acidic compound. The polysaccharide or oligosaccharide may be co-cross-linked with a protein such as keratin/collagen or elastase. The vector may be prepared by reacting succinic acid monochloride in aqueous solution with a cross-linked polysaccharide or oligosaccharide matrix to graft succinic acid onto the matrix to form the nucleus, grinding the nucleus to a size between 10 nm and 10 .mu.m, drying the ground nucleus, coupling fatty acid compounds to the nucleus to form a first layer and hydrophobically bonding phospholipids to the first layer to form a second layer. The succinic acid monochloride is preferably prepared by reacting succinic acid dichloride with free succinic acid to form pure crystalline succinic acid monochloride.

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Toulouse, France

Jaouad Meniali