English Translation

Preparation Process of Drug-Eluting Stent (DES) and Drug-Coated Balloon (DCB)

The preparation processes of Drug-Eluting Stent (DES) and Drug-Coated Balloon (DCB) cover core procedures including substrate forming, surface treatment, and drug coating. The precise control of process details directly determines the device performance and clinical safety. This article fully decomposes the preparation workflows of the two types of devices, clarifying the technical key points and core differences of each procedure.

Both DES and DCB preparation involve substrate fabrication, surface treatment, drug coating, drying and curing, quality inspection, sterilization and packaging. Their core differences lie in substrate forming, drug coating technology and parameter control.

1 Preparation Process of Drug-Eluting Stent (DES)

1.1 Fabrication of Metallic Stent

① Material Selection:

Medical grade 316L stainless steel: A traditional material with low cost but poor flexibility.
Cobalt-chromium alloy (e.g., L605, MP35N): High strength and corrosion resistance, suitable for thin-wall design.
Platinum-chromium alloy (e.g., PtCr): Excellent X-ray radiopacity and superior mechanical properties.
Bioabsorbable materials (e.g., PLLA polylactic acid): Applied for biodegradable stents that gradually degrade in vivo.

② Stent Forming Technology:

Laser Cutting: Ultrashort pulsed laser (e.g., femtosecond laser) is used to cut mesh structures on metal tubes with micron-level precision. It adapts to complex designs such as spiral support and open-cell structures, ensuring smooth cutting edges and reducing thrombosis risk.
Electrolytic Polishing: Electrochemical treatment removes burrs generated by laser cutting, improves surface smoothness, and mitigates inflammatory reactions.
Heat Treatment: Annealing is performed on cobalt-chromium alloys to eliminate internal stress and enhance flexibility as well as radial supporting force.

1.2 Surface Treatment and Functionalization

Surface Roughening: Sandblasting (bombarding the stent surface with micron-sized alumina particles to increase roughness) and acid etching (chemical corrosion via mixed nitric-hydrofluoric acid solution to form microporous structures), both adopted to improve coating adhesion.
Coating Underlayer Preparation: Plasma treatment (activating the metal surface to form hydroxyl or amino groups to facilitate chemical bonding of polymer coatings); intermediate layer coating (some stents are pre-coated with silicone or parylene underlayers to improve the uniformity of subsequent drug layers).

1.3 Design and Coating of Drug Layer

① Drug and Carrier Selection: Antiproliferative drugs include sirolimus, everolimus, paclitaxel, etc. Polymer carriers adopt degradable materials such as PLGA and PLLA, or non-degradable materials such as PVDF (biocompatibility needs optimization).

② Coating Technology:

Spray Coating: The drug-polymer solution is uniformly sprayed onto the stent surface via precision ultrasonic nozzles. Temperature, humidity and spraying speed are controlled to achieve adjustable coating thickness (usually 2-5 μm), suitable for multi-layer coating.
Dip Coating: The stent is immersed in drug solution, with coating thickness controlled by pulling speed. Its disadvantage is drug accumulation at edges, requiring secondary finishing.
Electrospinning: An innovative process (effectiveness not fully verified), which can form nanofiber membranes on the stent surface to increase drug loading and sustained-release performance.

1.4 Drying and Curing

Vacuum Drying: Removes solvents to avoid drug crystallization and coating cracking.
UV Curing: Cross-links photosensitive polymers to enhance coating stability.
Oven Drying: Low-temperature drying is adopted to protect drug activity.

1.5 Quality Control and Inspection

Coating Uniformity Inspection: Scanning Electron Microscopy (SEM) is used to observe coating morphology and detect cracks or bubbles; Atomic Force Microscopy (AFM) analyzes coating thickness and roughness with nanometer-level precision.
Drug Release Test: In vitro simulation test (immersing stents in PBS phosphate buffer solution). High Performance Liquid Chromatography (HPLC) is applied to determine drug release at different time points and verify whether the sustained-release curve meets design requirements (e.g., 80% drug release within 30 days).
Mechanical Performance Test: Radial strength test (simulating vascular pressure to assess compression resistance); flexibility test (evaluating the deliverability through tortuous blood vessels via bending tests).

1.6 Sterilization and Packaging

Low-temperature ethylene oxide gas sterilization is adopted to prevent high temperature from damaging drug activity. Vacuum sealed packaging is applied to avoid coating instability caused by moisture and oxygen.

2 Preparation Process of Drug-Coated Balloon (DCB)

2.1 Material Selection

Balloon Material: Polymer materials such as nylon and polyurethane are commonly used, featuring good flexibility and biocompatibility.
Drug Selection: Mainly antiproliferative drugs (e.g., paclitaxel). The drugs must comply with principles of efficacy, stability, controlled release performance, biocompatibility, carrier compatibility and dosage compliance, with clinical verification and safety assessment completed.

2.2 Balloon Forming

Substrate fabrication of balloon is completed by means of extrusion molding (extruding materials into tubular shape) and blow molding (heating tubular materials and blowing into balloon shape) with a balloon forming machine.

2.3 Drug Spraying Preparation (Core Procedure)

Core workflow: Balloon surface pretreatment → Drug solution preparation → Spraying equipment commissioning → Precision spraying → Solvent evaporation / Drying and curing → Post-treatment and quality inspection.

Balloon Surface Pretreatment: To enhance the adhesion between coating and balloon material. Common methods include plasma treatment (argon/oxygen surface activation, treatment time: 30s-5min, power: 50-200W) and chemical primer coating (applying polyurethane or silane coupling agent intermediate layer).
Drug Solution Preparation: Divided into carrier-free scheme (paclitaxel dissolved in organic solvents such as acetone and tetrahydrofuran, concentration: 1-5 mg/ml) and carrier blending scheme (paclitaxel mixed with iohexol, PVP and other carriers using water-ethanol mixed solvent). Viscosity is controlled at 10-30 CPS, and surface tension optimized by adding Polysorbate 80.
Spraying Equipment Selection: Ultrasonic spraying is the mainstream technology (high-frequency vibration atomizes liquid into micron-sized droplets, frequency: 20-120 kHz, flow rate: 0.001-1 mL/min). Pressure spraying features higher efficiency (high-pressure gas atomization, air pressure: 0.2-0.8 MPa). Rotational spraying or multi-axis linkage control is required for complex balloons.
Spraying Parameter Optimization: Spraying speed: 0.1-0.5 mm/s; spraying times: 3-8 times (single-layer thickness: 0.5-2 μm); ambient temperature: 20-25°C, humidity: <30% RH. Closed-loop feedback system can realize real-time thickness adjustment (not yet widely applied).

2.4 Drying and Curing

Coating solvents are removed under controlled temperature and humidity, and coatings are cured by heat treatment or ultraviolet irradiation to ensure stable drug adhesion.

2.5 Quality Inspection

It includes visual inspection (defect-free), drug content detection (compliant with standards), and mechanical performance test (expansion performance and structural strength).

2.6 Sterilization and Packaging

Ethylene oxide or gamma ray sterilization is adopted, followed by sealed packaging in a sterile environment to prevent contamination.

The preparation processes of DES and DCB are differentially designed according to their respective device characteristics. Every procedure from material selection to sterilization and packaging needs to balance drug efficacy retention, mechanical properties and biocompatibility. Standardized preparation procedures are the core guarantee for stable quality, clinical safety and effectiveness of drug-coated interventional devices.