TY - JOUR
T1 - Controlled release implants for cardiovascular disease
AU - Levy, Robert J.
AU - Johnston, Thomas P.
AU - Sintov, Amnon
AU - Golomb, Gershon
PY - 1990/1
Y1 - 1990/1
N2 - 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.
AB - 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.
KW - arrhythmia
KW - calcification
KW - controlled release implants
KW - pacemaker
KW - sustained release preparation
UR - http://www.scopus.com/inward/record.url?scp=0025159222&partnerID=8YFLogxK
U2 - 10.1016/0168-3659(90)90137-I
DO - 10.1016/0168-3659(90)90137-I
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AN - SCOPUS:0025159222
SN - 0168-3659
VL - 11
SP - 245
EP - 254
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1-3
ER -