Major advances have been made in the past few decades in the percutaneous treatment of artery diseases. The development of each new technology has been spurred by the downfall of the previous technology. Balloon angioplasty emerged as a minimally invasive solution to previous treatment methods that typically involved significant opportunity for complications. This treatment method came with its own disadvantages due to its inability to prevent vessel recoil and neointimal proliferation.
Intracoronary stenting through Bare Metal Stents (BMS) overcame the acute recoil of balloon angioplasty, but was unable to prevent the occurrence of instent-restenosis (ISR) caused by excessive neointimal proliferation.
Drug-Eluting Stents (DES) utilize agents that effectively reduce the occurrence of this neointimal proliferation and increase or eliminate the time needed for subsequent treatment. The agents consist of an antiproliferative drug and a specially designed polymer coating to control the release profile of the drug over time. Ultrasonic Atomization technology has proven successful in the application of these agents on to DESs.
Even with the benefits provided by DESs, it is still important to address its drawbacks. The antiproliferative drugs are not able to completely eliminate the possibility of ISR and may react to the drug or polymer coating. Managing restenosis of an installed stent becomes extremely difficult. Revascularization techniques coupled with antiproliferative drug delivery is necessary for successful treatment of this condition.
Drug-Eluting Balloons (DEBs) have emerged in recent years as a successful treatment alternative for restenosis and other forms of arterial diseases. The idea of delivering antiproliferative drugs to the site of an interventional procedure has existed for some time. However, the successful development of BMS coupled with their easy application inside the body took priority over developing effective transfer methods. Even though DEB is a relatively new technology, there are significant benefits that these devices can offer. Driven by the limitations of DESs, DEBs are still able to deliver the important antiproliferative drugs necessary to prevent restenosis without the use of a stent. For diseased areas where a stent may not be applied, such as in small vessels, tortuous vessels, or calcified lesions, DEBs can provide treatment.
Other advantages include rapid release and homogenous transfer of the drug to the vessel wall and the absence of both stent and polymer, allowing the original anatomy to remain intact and reducing the chance of chronic inflation or late thrombosis.
DEB Technology and Coating Requirements
The purpose of these DEBs is to deliver antiproliferative drugs to the cell walls. Although the method of accomplishing this feat varies between manufacturers, there are some similarities. The lasting effect of paclitaxel coupled with its quick uptake into vascular cells makes it the drug of choice in this application across the board.
The DEB catheters are required to travel through significant lengths of blood vessels before reaching the point of delivery. It is most often necessary to protect the paclitaxel in some type of binder during travel through the body. In many of the DEBs currently undergoing clinical trials, the paclitaxel is interspersed in a hydrophilic matrix, allowing the coating to swell during travel through the body and allowing the release of the paclitaxel upon inflation of the balloon catheter. The coating should also maximize the amount of paclitaxel released from the hydrophilic matrix.
The characteristics of this coating are extremely important in making DEBs successful. DEBs claim to deliver a homogenous application of drug to the vessel walls at a fast rate, typically less than one minute. Other factors for success include the amount of drug delivered and maintaining a uniform surface concentration.
Alternative Methods for Coating DEBs
Several different coating technologies are possible for the application of these drug/binder combinations onto the balloons. The balloon can be coated using ultrasonic atomization, dip coating of the balloon into a liquid bath, and pipetting the liquid onto the device.
Each method has its own benefits and disadvantages. As previously discussed, the ideal equipment for DEB coatings should meet the following criteria:
(1) Coating Uniformity: Minimal variance across the full length and diameter of balloon.
(2) Repeatability: Coating method must be able to maintain consistent application both in coating morphology and uniformity from balloon to balloon.
(3) Compatibility with chemicals: Coating technology must be proven to not damage or degrade the drug or polymer performance and will not fail due to chemicals or solvents used.
(4) Process Variables: Independent and easy process variable control is necessary for process and coating development and optimization. Results of this include the ability to easily change coating thickness or morphology.
(5) Minimal Operator Intervention necessary for maintaining or cleaning coating equipment to minimize possible contamination.
One of the possible coating technologies that meets all of these criteria is Ultrasonic Atomization.
Ultrasonic Atomization technology is a very high-tech atomization technique that is used for spray coating. As shown in Fig. 1, the liquid is fed through the center of the nozzle, allowing unrestricted flow out of the orifice, and creating a thin liquid film on the surface of the nozzle. As this surface is set to vibrate at a certain frequency perpendicular to the film, the liquid absorbs the vibrational energy and standing waves are created. These standing waves form a mathematically definable array of crests and troughs depending on the characteristics of the liquid and the frequency that the surface is vibrating at.