Implantable drug delivery systems formulated from drug-polymer composites have been used recently in a variety of applications in which chronic administration of a pharmacological agent to a specific anatomic site is advantageous. These drug delivery systems are generally referred to as controlled release matrices.' Their mechanism of drug release involves either passive drug diffusion, or biodegradation of the polymer matrix, or both. This review considers only those devices that are implanted at the drug target site, and not those that dispense drugs systemically. The advantages of sitespecific controlled release implants are that a substantially lower dose of the drug is required, since it is administered at an optimal location, and therefore the risks for systemic side effects are greatly reduced.
A controlled release implant, in widespread clinical use, is the dexamethasone-silicone rubber matrix configured for insertion in a cardiac pacing electrode tip. Al- though cardiac pacemakers have been utilized for the past 30 years, a persistent clinical problem has been the time-dependent progressive increase in the pacemaker electrode's electrical capture thresholds due to fibrosis. Dexamethasone is an antiinflammatory, antifibrotic synthetic steroid. The working hypothesis of the controlled release dexamethasone approach is that sustained release steroid administered directly to the endocardium contacting the electrode would limit acute inflammation and chronic inflammation, as well as the resultant scarring, that adversely affect electrical capture thresholds.
Several clinical studies have demonstrated the improved pacing threshold characteristics of a steroideluting electrode. A double-blinded study2 compared the same electrode configuration (Medtronic, Minneapolis, MN) with and without steroid over a 2-year follow-up period. The results showed that from 2 weeks to 2 years the pulse duration thresholds for the steroid leads remained almost constant, while the nonsteroid cases demonstrated a significant rise in thresholds. A more recent double-blinded clinical study has confirmed these findings over a 6-month follow-up p e r i ~d . ~ Thus, the steroid-eluting cardiac pacing lead represents an important example of an effective clinical use of a controlled release drug implant.