A water-loving drug modified with a hydrophobic fatty acid tail has been found to self-assemble into a hydrogel that can enmesh a second agent. The hydrogel can then be dissolved enzymatically, enabling it to serve as a two-agent delivery vehicle (Biomaterials, DOI: 10.1016/j.biomaterials.2008.09.045). "To the best of our knowledge, there are no previous reports on developing single and multiple drug-delivery vehicles from self-assembled prodrugs," note Jeffrey M. Karp of Brigham & Women's Hospital, in Boston; George John of the City College of New York; and coworkers, who carried out the study. The researchers derivatized acetaminophen with a fatty acid. This turns the drug into an amphiphilic prodrug that self-assembles into a hydrogel. The researchers showed that the hydrogel can encapsulate a second agent, the anti-inflammatory agent curcumin. Exposure to lipase degrades the hydrogel, releasing the two agents; the nontoxic fatty acid is a by-product. "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," the researchers write.