Method of manufacturing polymer-free everolimus-eluting coronary stent fabricated by electrospinning technique

1. A method of manufacturing a drug-eluting stent, the method comprising:

a) forming a nitrogen-doped titanium oxide layer on a surface of a stent;

b) introducing a surface-binding functional group including a hydroxyl group onto the titanium oxide layer to perform surface-modification;

c) preparing an everolimus-based drug of which a carboxylic acid group is formed at an end; and

d) electrospinning a mixture containing the everolimus-based drug of which a carboxylic acid group is formed at an end and a solvent on the surface-modified titanium oxide layer,

wherein the drug-eluting stent contains the everolimus-based drug bound onto the stent via an ester bond and the everolimus-based drug physically attached to the stent, but does not contain a polymer

wherein the everolimus-based drug of which the carboxylic acid group is formed at the end is prepared by mixing an everolimus-based drug represented by the following Chemical Formula 1 and an organic acid in an alcohol solvent

2. The method of claim 1 , wherein the drug-eluting stent satisfies the following Correlation Equation 1:

R 7d /R A ≤0.85  Correlation Equation 1

here, R 7d is a cumulative elution amount of the everolimus-based drug eluted from the drug-eluting stent in a phosphate buffer saline solvent at pH 7.4, 37° C. and 100 rpm for 7 days, R A is a total loading amount of the everolimus-based drug loaded on the stent, and the unit of the cumulative elution amount and the total loading amount is a mass unit.

3. The method of claim 2 , wherein the drug-eluting stent satisfies the following Correlation Equation 2:

R 1d /R A ≤0.3  Correlation Equation 2

here, R 1d is a cumulative elution amount of the everolimus-based drug eluted from the drug-eluting stent in the phosphate buffer saline solvent at pH 7.4, 37° C. and 100 rpm for 1 day, R A is the total loading amount of the everolimus-based drug loaded on the stent, and a unit of the cumulative elution amount and the total loading amount is a mass unit.

4. The method of claim 1 , wherein the surface-binding functional group is formed on the nitrogen-doped titanium oxide layer by surface-treatment with low-temperature plasma, and the nitrogen-doped titanium oxide layer satisfies the following Correlation Equation 3:

θ s /θ 0 ≤0.80  Correlation Equation 3

here, θ s is a contact angle of water with respect to the titanium oxide layer surface-treated with the low-temperature plasma, and θ 0 is a contact angle of water with respect to a nitrogen-doped titanium oxide layer that is not surface-treated with the low-temperature plasma.

5. The method of claim 1 , wherein the solvent is acetonitrile.

6. The method of claim 1 , wherein the mixture further contains any one or more promoters selected from the group consisting of 4-dimethylaminopyridine and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide.

7. The method of claim 1 , wherein the everolimus-based drug of which the carboxylic acid group is formed at the end is Represented by the following Chemical Formula 2;