Controlled release implants for cardiovascular disease

Abstract

The systemic therapy of many cardiovascular diseases is often hampered by adverse drug effects. The present paper examines the use of controlled release implants as a means for optimizing drug concentrations at the affected site in the cardiovascular 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 as poly(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 tachycardia to normal sinus rhythm in dogs. A matrix system containing gentamicin has been used by others [35] to prevent experimental valvular endocarditis. Other workers have used a dexamethasone-releasing cardiac pacing lead in clinical studies, to prevent scar tissue formation, which leads to elevated electrical pacing threshold [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.