Self-assembled prodrugs: an enzymatically triggered drug-delivery platform

Biomaterials. 2009 Jan;30(3):383-93. doi: 10.1016/j.biomaterials.2008.09.045. Epub 2008 Oct 17.


Enzyme catalysis as a tool to disassemble supramolecular hydrogels to control the release of encapsulated drugs provides an opportunity to design a wide range of enzyme-specific low-molecular-weight hydrogelators. In this proof-of-concept work, we report the synthesis of low-molecular-weight amphiphilic prodrugs as hydrogelators from a well-known drug acetaminophen (which belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers)). We have shown the ability of prodrugs to self-assemble to form hydrogels that could subsequently encapsulate a second drug such as curcumin, which is a known chemopreventive and anti-inflammatory hydrophobic drug. Upon enzyme-triggered degradation, the hydrogel released single or multiple drugs at physiologically simulated conditions in vitro. Given that the degradation products consist of the drug and a fatty acid, this approach has an advantage over polymer-based prodrugs that generate polymer fragments with heterogeneous chain lengths upon degradation that may present complex toxicity profiles. Additionally, drug-release occurred without burst release. Spectrophotometric experiments supported the drug-release, and the rate was controlled by modulation of temperature and enzyme concentration. Mesenchymal stem cells treated with prodrugs retained their stem cell properties including the capacity of multi-lineage differentiation, and maintained their adhesive and proliferation capacities with high viability. The present biomaterials could have broad applications as drug-delivery vehicles and cell invasive matrices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / pharmacology
  • Drug Delivery Systems*
  • Humans
  • Hydrogels / chemistry
  • Lipase / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Microscopy, Electron, Scanning
  • Models, Molecular
  • Phenotype
  • Prodrugs / pharmacology*


  • Hydrogels
  • Prodrugs
  • Acetaminophen
  • Lipase