ATTEMPTS: A heparin/protamine-based triggered release system for the delivery of enzyme drugs without associated side-effects

Yoon Jeong Park, Jun Feng Liang, Hui Song, Yong Tao Li, Sarita Naik, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)251-265
Number of pages15
JournalAdvanced Drug Delivery Reviews
Volume55
Issue number2
DOIs
StatePublished - 10 Feb 2003

Keywords

  • ATTEMPTS
  • Biologic conjugation
  • Chemical conjugation
  • Enzyme drug
  • Heparin
  • Prodrug
  • Protamine

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