Drug Release Kinetics From Stent Device-Based Delivery Systems

Abstract

In an effort to overcome the limitations of balloon-expandible intravascular metal stent-induced neointimal formation, drug-coated stent devices have been developed. The stent platform allows the local delivery of drugs to an injury site, thereby reducing the amount of drug exposure to the systemic circulation and other organs. The drug carrier matrix allows the release of the drug in a diffusion-controlled manner over an extended time period after the stent implant. The drugs are chosen such that the complex cascade of events that occurs after stent implantation that leads to smooth muscle cell proliferation and migration towards the intima are inhibited. The success of an antirestenotic drug therapy from a drug-coated stent is dependent, at least partially, on the extent of drug elution from the stent, the duration and rate of release, and accumulation of drug in the arterial wall in such a way that it covers the initiation and progression of vessel wall remodeling. The local vascular drug concentrations achieved are directly correlated with the biological effects and local vascular toxicity, and there is therefore a challenge in finding an optimum dose of drug to be delivered to tissues (ie, one that has the desired therapeutic effect without local adverse effects). There is increased focus on optimization of various factors that affect drug release from the stent system, including the physicochemical properties of the drugs, carrier vehicle formulation, and profile of elution kinetics. This review highlights the various factors involved in drug release kinetics, local vascular toxicity, carrier vehicle matrix, tissue deposition, and distribution through the arterial wall from stent-based drug delivery systems.