Polymeric drug delivery systems for treatment of cardiovascular calcification, arrhythmias and restenosis

Abstract Cardiovascular controlled release, utilizing drug-polymer composites implanted in direct contact with the heart, has recently come into clinical use with a dexamethasone eluting cardiac pacemaker lead tip. Furthermore, cardiovascular controlled release systems are under active investigation in a number of other areas of possible application. The general working hypothesis of this approach is that regionally administered drug delivered directly to the heart or a blood vessel will more efficiently and effectively treat localized disease processes of interest, while avoiding systemic side effects. Successful experimental examples illustrating the validity of this hypothesis have involved investigations into cardiovascular calcification, therapy of cardiac arrhythmias, and treatment of arterial restenosis following angioplasty. Efficacious results in each of these areas, with some limitations, have been noted, and are discussed in detail in this paper. An ideal cardiovascular controlled release system will consist of a feedback responsive implant in which drug release kinetics could be varied according to disease activity, or other considerations such as side effects of the therapeutic agent. Furthermore, cardiovascular drug delivery should be ideally extremely long acting and this may be possible through the use of therapeutic agents in a refillable reservoir configuration, or local gene therapy with long standing expression of the gene of interest.