Drug-eluting catheter and method of manufacturing the same

1. An expandable drug-eluting catheter, comprising:

an expandable portion having a surface;

a first coating on the surface of the expandable portion, the first coating comprising a negatively charged resin; and

a second coating on the surface of the expandable portion, wherein the first coating is between the surface and the second coating, the second coating comprises a polymeric surface active agent and biocompatible nanoparticles, the biocompatible nanoparticles are formed in layers and in contact with each other, and the nanoparticles are positively charged and entrap a bioactive substance.

2. The drug-eluting catheter of claim 1 , wherein the negatively charged resin is formed from any compound selected from the group consisting of a polycarboxylic acid, an acid anhydride of a polycarboxylic acid, or an ester of a polycarboxylic acid.

3. The drug-eluting catheter of claim 2 , wherein the polycarboxylic acid is one or more selected from the group consisting of polymers of acrylic acid, methacrylic acid, maleic acid, fumaric acid, aspartic acid and glutamic acid; a carboxymethyl substituted starch, cellulose or polyvinyl alcohol; alginic acid; and pectin.

4. The drug-eluting catheter of claim 2 , wherein the acid anhydride or ester of polycarboxylic acid is an acid anhydride or ester of a polymer of acrylic acid, methacrylic acid or maleic acid.

5. The drug-eluting catheter of claim 4 , wherein the acid anhydride of polycarboxylic acid is a maleic anhydride copolymer.

6. The drug-eluting catheter of claim 5 , wherein the maleic anhydride copolymer is one or more selected from the group consisting of a maleic anhydride-methyl vinyl ether copolymer, a maleic anhydride-styrene copolymer and a maleic anhydride-ethylene copolymer.

7. The drug-eluting catheter of claim 1 , wherein the biocompatible nanoparticles are positively charged by adhering a cationic polymer to the surface.

8. The drug-eluting catheter of claim 7 , wherein the cationic polymer is a chitosan.

9. The drug-eluting catheter of claim 1 , wherein the biocompatible nanoparticles are formed of any compound selected from the group consisting of polylactic acid, polyglycolic acid, a lactic acid-glycolic acid copolymer and a lactic acid-aspartic acid copolymer.

10. The drug-eluting catheter of claim 1 , wherein the bioactive substance is a nucleic acid compound.

11. The drug-eluting catheter of claim 10 , wherein the nucleic acid compound is one or more selected from the group consisting of a plasmid DNA, a gene, a decoy, an siRNA, an oligonucleotide, an antisense oligonucleotide, a ribozyme and an aptamer.

12. The drug-eluting catheter of claim 11 , wherein the nucleic acid compound is an NFκB decoy oligonucleotide.

13. The drug-eluting catheter of claim 12 , wherein the NFκB decoy oligonucleotide is one selected from SEQ ID NO. 1, SEQ ID NO. 2 and SEQ ID NO. 3.

14. A method of treating a vascular stenosis or a dialysis shunt stenosis, comprising:

inserting the drug-eluting catheter of claim 12 into the stenosis in a blood vessel, and

expanding the expandable portion,

wherein the bioactive substance is subsequently released from the expandable portion, thereby treating the vascular stenosis or dialysis shunt stenosis.

15. The drug-eluting catheter of claim 1 , wherein the drug-eluting catheter is a balloon catheter having a balloon as the expandable portion.

16. The drug-eluting catheter of claim 15 , wherein a recess is formed in a surface of the balloon.

17. The drug-eluting catheter of claim 16 , wherein the recess is circular or elliptical.

18. A method of manufacturing the drug-eluting catheter of claim 1 , the method comprising:

a nanoparticle formation step of

adding a mixed solution of at least a solution of bioactive substance and a solution obtained by dissolving a biocompatible polymer in an organic solvent to an aqueous solution obtained by dissolving at least a cationic polymer;

entrapping the bioactive substance into the biocompatible polymer and generating a suspension of a biocompatible nanoparticle whose surface is positive-charge-modified by adding the mixed solution into an aqueous solution comprising a cationic polymer and a surface active agent;

a negative-charge-modification step of negative charge-modifying an expandable portion of a catheter main body by coating the expandable portion surface with a negatively-charged resin;

a nanoparticle adherence step of forming a nanoparticle layer by adhering the biocompatible nanoparticle to the negative-charge-modified expandable portion; and

a drying step of drying the nanoparticle layer.

19. The method of claim 18 , wherein the negative-charge-modification step is performed by dipping the expandable portion in a solution of a polycarboxylic acid or a polycarboxylic acid derivative.

20. The method of claim 18 , wherein an anionic bioactive substance is further added to the suspension of the biocompatible nanoparticle.

21. The method of claim 18 , wherein the nanoparticle adherence step is repeated a plurality of times to further place a nanoparticle layer on the nanoparticle layer formed on the expandable portion.

22. The method of claim 21 , wherein the nanoparticle adherence step is repeated a plurality of times to form the nanoparticle layers of biocompatible nanoparticles entrapping different bioactive substances one on top of another or in a mosaic pattern.

23. The method of claim 18 , the method further comprising:

an impregnation step of impregnating the nanoparticle layer with a solution of a biodegradable polymer.

24. The method of claim 23 , wherein, in the impregnation step, the bioactive substance is further added to the solution of the biodegradable polymer.

25. The method of claim 23 , wherein the biodegradable polymer with which the nanoparticle layer is impregnated in the impregnation step degrades in vivo more rapidly than the biocompatible polymer forming the biocompatible nanoparticle.