TY - JOUR
T1 - The ATTEMPTS delivery systems for macromolecular drugs
AU - Kwon, Young Min
AU - Li, Yongtao
AU - Naik, Sarita
AU - Liang, Jun Feng
AU - Huang, Yongzhuo
AU - Park, Yoon Jeong
AU - Yang, Victor C.
PY - 2008/11
Y1 - 2008/11
N2 - Aiming at successful targeted drug delivery - a system that possesses both targeting and prodrug features that can be activated once the system reaches the target site upon systemic administration - would be desired to reduce systemic toxicity. Previously we proposed a heparin/ protamine-based system for delivery of protease drugs such as tissue-specific plasminogen activator (t-PA). This approach, termed 'antibody targeted, triggered, electrically modified prodrug-type strategy' (ATTEMPTS), would permit antibody-directed administration of inactive t-PA and allow a subsequent triggered release of the active t-PA at the target site. This system can be adapted to target tumor tissues when protein transduction domain (PTD) peptide such as TAT is incorporated in the ATTEMPTS construct. Both in vitro and preliminary in vivo studies using TAT-gelonin (TAT-Gel) and TAT-asparaginase (TAT-ASNase) conjugates have demonstrated that the on/off regulation of the membrane translocation activity of PTD at tumor target, followed by intracellular delivery of cytotoxic macromolecular drug, can be accomplished. Hence, the PTD-mediated delivery system derived from our previous ATTEMPTS approach is a system that incorporates all of the targeting function, prodrug feature, release mechanism and cell entry mechanism and could become a generic system for delivery of macromolecular drugs.
AB - Aiming at successful targeted drug delivery - a system that possesses both targeting and prodrug features that can be activated once the system reaches the target site upon systemic administration - would be desired to reduce systemic toxicity. Previously we proposed a heparin/ protamine-based system for delivery of protease drugs such as tissue-specific plasminogen activator (t-PA). This approach, termed 'antibody targeted, triggered, electrically modified prodrug-type strategy' (ATTEMPTS), would permit antibody-directed administration of inactive t-PA and allow a subsequent triggered release of the active t-PA at the target site. This system can be adapted to target tumor tissues when protein transduction domain (PTD) peptide such as TAT is incorporated in the ATTEMPTS construct. Both in vitro and preliminary in vivo studies using TAT-gelonin (TAT-Gel) and TAT-asparaginase (TAT-ASNase) conjugates have demonstrated that the on/off regulation of the membrane translocation activity of PTD at tumor target, followed by intracellular delivery of cytotoxic macromolecular drug, can be accomplished. Hence, the PTD-mediated delivery system derived from our previous ATTEMPTS approach is a system that incorporates all of the targeting function, prodrug feature, release mechanism and cell entry mechanism and could become a generic system for delivery of macromolecular drugs.
KW - ATTEMPTS approach
KW - Prodrug
KW - Protein transduction domain (PTD) peptide
KW - Targeting
UR - http://www.scopus.com/inward/record.url?scp=57049170932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57049170932&partnerID=8YFLogxK
U2 - 10.1517/17425240802498059
DO - 10.1517/17425240802498059
M3 - Review article
C2 - 18976135
AN - SCOPUS:57049170932
SN - 1742-5247
VL - 5
SP - 1255
EP - 1266
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 11
ER -