Polymeric Drug Encapsulation on Stents  

The basic mechanism of drug delivery from a polymeric scaffold involves encapsulating a drug in a polymer that either allows the drug to diffuse outward from it or that undergoes degradation in order to release the drug directly. Polymers can be subdivided into bioerodable and nonbioerodable categories. The bioerodable polymers can be further subdivided into either bulk or surface erosion. [1]

Generally, for long term applications, such as in stents, a nonerodable polymer is used. This is because the fragments that break off from the polymer coating, particularly in polymers that undergo bulk erosion, tend to be phagocytosed by macrophages and other lymphocytes. Phagocytosis of polymer fragments can trigger macrophage activation, which release inflammatory cytokines, leading to increased lymphocyte infiltration of the site leading to inflammation. Numerous polymer systems that seemed promising in vitro have subsequently been abandoned after in vivo studies demonstrated inflammatory responses to them. Generally nonbioerodable, or biostable, polymers are used in more permanent biological applications, like stents, because of the potential for bioincompatibilty in erodable polymers cause and the more gradual release of drug that erodable polymers provide. [2]

Diffusion is the principal mechanism by which drugs are released from stents. [3] The mechanism of sirolimus release from the CYPHER stent will be explored in some depth in the next section. Though the TAXUS stent uses a similar approach, less information is available about it so CYPHER will be used as the model.

CYPHER Design and Manufacturing Techniques

The CYPHER stent is composed of a three layers of polymers over a frame made of laser cut 316L stainless steel. This metal stent is electropolished and coated in a primer layer of Parylene C. A mixture of polyethylene-co-vinyl acetate (PEVA) and poly n-butyl methacrylate (PBMA) in then dissolved in THF, which is a solvent suitable for dissolving organic molecules. This copolymer of PBMA to PEVA is 67% PEVA, 33% PBMA. Sirolimus is then dissolved in the THF/polymer mixture and the mixture is applied to the Parylene C coated stent. Another mixture of PEVA and PBMA, without sirolimus, is dissolved in THF and applied to the stent by spraying with a fine nozzle. This outer coating prevents the so-called “burst effect” which results when drug on the surface of the polymer is rapidly released following immersion in water or another solvent. (Small amount of sirolimus migrates to the final layer during this step because it dissolves in the THF and precipitates in the PEVA/PBMA outer layer. This causes a small but noticeable burst effect.[4]) The entire three layered coating is applied to both the luminal and abluminal sides of the stainless steel stent. Finally, the stent is placed on a delivery catheter, sterilized, and packaged. [5]