Enzyme responsive acetaminophen hydrogels

Utilization of enzyme catalysis as a tool to disassemble self-assembled hydrogels to control the release encapsulated drug provides an opportunity to design a wide range of enzyme-specific low-molecular-weight hydrogelators (LMWGs). Herein, we report a novel approach for controlled delivery of multiple drugs by an enzyme triggered hydrogel degradation mechanism. In this proof-of-concept work, we report the synthesis of LMWGs (amphiphiles) from well-known drug acetaminophen (which is known as Tylenolreg), and their ability to self-assemble into nanoscale structures in aqueous solutions to form hydrogels that subsequently encapsulate a second drug such as curcumin which is a known chemopreventive hydrophobic drug. Upon enzyme triggered degradation, hydrogels showed single and double drug delivery at physiological conditions in vitro. After treating with prodrug amphiphiles, mesenchymal stem cells (MSCs) retain their stem cell properties such as maintaining their adhesive and proliferation capacities with high viability. This new platform approach will have prospective effect on hydrogel based drug delivery research through developing drug delivery vehicles from a wide range of prodrug-based gelators.