The ATTEMPTS delivery systems for macromolecular drugs

Young Min Kwon, Yongtao Li, Sarita Naik, Jun Feng Liang, Yongzhuo Huang, Yoon Jeong Park, Victor C. Yang

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1255-1266
Number of pages12
JournalExpert Opinion on Drug Delivery
Volume5
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • ATTEMPTS approach
  • Prodrug
  • Protein transduction domain (PTD) peptide
  • Targeting

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