Polysaccharide-and polypeptide-based block copolymers, vesicles constituted by these copolymers and use thereof

Patent metadata

Field	Value
Publication number	US-9403916-B2
Application number	US-200913126589-A
Country	US
Kind code	B2
Filing date	Oct 30, 2009
Priority date	Oct 30, 2008
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The invention relates to a new type of polysaccharide-block-polypeptide diblock copolymer which is bioresorbable or biodegradable and biocompatible, to a method for preparing same, to the micellar vesicles constituted of this copolymer, and to the use thereof for encapsulation, transport, vectorization, and targeting of molecules of interest.

First claim

The invention claimed is:

1. A micellar vesicle, comprising an amphiphilic polysaccharide-block-polypeptide diblock linear copolymer composed of a polysaccharide block of natural or synthetic saccharide units with a polypeptide block of natural or synthetic peptide units, wherein:
said polysaccharide block and said polypeptide block are joined by their ends;
said polysaccharide is hyaluronic acid;
said polypeptide block is hydrophobic; and
said vesicle encapsulates at least one molecule of interest,
said micellar vesicle being capable of targeting cellular receptors and to allow targeted release of the encapsulated molecule of interest by receptor mediated endocytosis.

2. The micellar vesicle according to claim 1 , wherein said diblock copolymer comprises from 5 to 100 saccharide units, and from 5 to 100 peptide units.

3. The micellar vesicle according to claim 1 , wherein the polypeptide, in which the amino acid of which it is constituted can be in the optically active form L or D or in the racemic form DL, is selected from the group consisting of poly(alanine), poly(isoleucine, poly(leucine), poly(methionine), poly(phenylalanine), poly(proline), poly(tryptophan), poly(valine), poly(benzyl glutamate), poly(alkyl glutamate), poly(trifluoroacetyl-Lysine), poly(sarcosine), poly(hydroxyethyl-asparagine), poly(hydroxyalkyl-asparagine), poly(hydroxyalkyl-aspartamide), poly(benzyl aspartate) and derivatives thereof.

4. The micellar vesicle according to claim 1 , wherein said polysaccharide is hydrophilic and said polypeptide is hydrophobic under physiological conditions.

5. The micellar vesicle according to claim 4 , wherein the polypeptide is selected from the group consisting of poly(γ-benzyl L-glutamate) and poly(ε-trifluoroacetyl-L-lysine).

6. The micellar vesicle according to claim 1 , wherein said at least one molecule of interest is selected from those molecules used for preventing or treating a pathology or for restoring a biological function, in vitro or in vivo, in an animal or on isolated cells.

7. The micellar vesicle according to claim 6 , wherein said molecule of interest is selected from the group consisting of an active ingredient of a medicament, a peptide, a protein, a hormone, an enzyme, a nucleic acid, an oligonucleotide, an antigen, an antibody, an interferon, a growth factor, a modulator of enzyme activity, a cell receptor activator or inhibitor, and a vitamin.

8. A pharmaceutical composition comprising a micellar vesicle according to claim 1 and a pharmaceutically acceptable excipient.

9. The micellar vesicle according to claim 1 , wherein the vesicle further comprises two compartments of different polarity.

10. The micellar vesicle according to claim 9 , wherein the vesicle has a hydrophobic membrane and a hydrophilic internal cavity.

11. The micellar vesicle according to claim 2 , wherein said diblock copolymer comprises from 10 to 50 saccharide units.

12. The micellar vesicle according to claim 2 , wherein said diblock copolymer comprises from 10 to 50 peptide units.

13. The micellar vesicle according to claim 2 , wherein said diblock copolymer comprises from 10 to 50 saccharide units and from 10 to 50 peptide units.

14. The micellar vesicle according to claim 6 , wherein said animal is a human.

Assignees

• Lecommandoux Sébastien
• Le Meins Jean-François
• Schatz Christophe
• Upadhyay Kamal Kumar
• Univ Bordeaux
• Inst Polytechnique Bordeaux

Inventors

• Lecommandoux Sébastien
• Le Meins Jean-François
• Schatz Christophe
• Upadhyay Kamal Kumar

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K8/14

  Liposomes; Vesicles · CPC title

• A61K9/1273

  Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances · CPC title

• C08G81/00

  Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42}) · CPC title

• C08B37/00 Primary

  Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof (cellulose D21; {microbiological processes C12P}) · CPC title