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

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. Published by Elsevier Ltd.