Controlled Release Implants for Cardiovascular Disease*

The systemic therapy of many curd~ou~cu~r diseases is often hampered by uduerse drug effects. The present paper examines the use of ~ontro~~d release implunts as a mean for optimizing drug concentrations at the affected site in the ~ard~v~~u~r system, while using a relatively low systemic dose. Controlled release systems have been prepared by combining a drug of choice with either a non-degradable polymer, such as a silicone rubber, polyurethane, and ethylene vinylacetate, or a biodegradable compound such aspoly(glycolic-lactic acid) or a high molecular weight polyanhydride. Controlled release matrices containing ethylenehydroxydiphosphonate (EHDP), when implanted next to a bioprosthetic heart valve leaflet, prevented pathologic calcification. Similarly, controlled release matrices containing lidocaine-HCl have been used experimentally as epicardial implants to convert ventricular taehycardia to normal sinus rhythm in dogs. A matrix system containing gentamic~n has been used by others [35] to prevent experimental valvular endo~ardit~. stir workers have used a dexamet~one-rele~ing ~urd~c pacing lead in clinical studies, to prevent scar tissue format~n, which leads to e~vated e~~trical~~~ thres~~ [15,16]. Future controlled release systems for cardiovascular use will very likely incorporate innovative design features including: a reservoir configuration to replenish or change drug therapy, modulatable drug release to vary drug dosing as desired, and closed-loop feedback to increase or decrease release rates in response to disease status.