TY - JOUR
T1 - ATTEMPTS
T2 - A heparin/protamine-based triggered release system for the delivery of enzyme drugs without associated side-effects
AU - Park, Yoon Jeong
AU - Liang, Jun Feng
AU - Song, Hui
AU - Li, Yong Tao
AU - Naik, Sarita
AU - Yang, Victor C.
PY - 2003/2/10
Y1 - 2003/2/10
N2 - A prodrug type delivery system based on competitive ionic binding for the conversion of the prodrug to an active drug has been developed for delivery of enzyme drugs without their associated toxic side-effects. This approach, termed "ATTEMPTS" (antibody targeted, triggered, electrically modified prodrug-type strategy), would permit the administration of an inactive drug and then subsequently triggered release of the active drug at the target site. The underlying principle was to modify the enzyme with small cationic species so that it could bind a negatively charged heparin-linked antibody, and the latter would block the activity of the enzyme drug until it reached the target. To provide the enzyme drug with appropriate binding strength to heparin, a cationic poly(Arg) 7 peptide was incorporated onto the enzyme either by the chemical conjugation method using a bifunctional crosslinker or by the biological conjugation method using the recombinant methodology. Methods for drug modification, heparin-antibody conjugation, and the prodrug and triggered release features of the "ATTEMPTS" approach are described in detail in this review article.
AB - A prodrug type delivery system based on competitive ionic binding for the conversion of the prodrug to an active drug has been developed for delivery of enzyme drugs without their associated toxic side-effects. This approach, termed "ATTEMPTS" (antibody targeted, triggered, electrically modified prodrug-type strategy), would permit the administration of an inactive drug and then subsequently triggered release of the active drug at the target site. The underlying principle was to modify the enzyme with small cationic species so that it could bind a negatively charged heparin-linked antibody, and the latter would block the activity of the enzyme drug until it reached the target. To provide the enzyme drug with appropriate binding strength to heparin, a cationic poly(Arg) 7 peptide was incorporated onto the enzyme either by the chemical conjugation method using a bifunctional crosslinker or by the biological conjugation method using the recombinant methodology. Methods for drug modification, heparin-antibody conjugation, and the prodrug and triggered release features of the "ATTEMPTS" approach are described in detail in this review article.
KW - ATTEMPTS
KW - Biologic conjugation
KW - Chemical conjugation
KW - Enzyme drug
KW - Heparin
KW - Prodrug
KW - Protamine
UR - http://www.scopus.com/inward/record.url?scp=0037428958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037428958&partnerID=8YFLogxK
U2 - 10.1016/S0169-409X(02)00181-3
DO - 10.1016/S0169-409X(02)00181-3
M3 - Article
C2 - 12564979
AN - SCOPUS:0037428958
SN - 0169-409X
VL - 55
SP - 251
EP - 265
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
IS - 2
ER -