Hydrogel Releases Drug in Two Steps

DRUG DELIVERY

A hydrogel-drug system that relies on the consecutive action of two trigger mechanisms to release a drug has the potential to target specific sites within the body, according to the scientists in the Netherlands who developed the system. The triggers are a stimulus that converts the gel into a solution and an enzyme that cleaves the hydrogelator-drug link.

"Raising the temperature or lowering the pH causes more low-molecular-weight gelator molecules to come out of the gel fibers and go into solution,"; says Kjeld J. C. van Bommel, a researcher at Biomade Technology Foundation, Groningen, who carried out the work with Jan van Esch, assistant professor of chemistry at the University of Groningen, and coworkers (Org. Biomol. Chem. 2005, 3, 2917).

"Only when they are in solution can the molecules be cleaved by an enzyme and the drug be released," van Bommel continues. "The combination of a low-molecular-weight gelator gel sensitive to both its environment and enzymes is unique. It demonstrates that such systems are viable for controlled drug delivery and presents an innovative approach to drug delivery system design in general."

The system devised by the group makes use of a cyclohexane trisamide gelator compound covalently connected to a model drug. The compound gels in water to form a dense network of long, straight, unbranched tubular fibers that protect the drug moiety from enzymatic cleavage before release. The group used 6-aminoquinoline as a model drug to demonstrate proof-of-concept of the system.

The system has a number of advantages over other two-stage drug delivery systems such as polymeric gelator systems, according to the team. First, the gels have rapid response times–on the order of a few seconds–that are not attainable by polymeric systems. In addition, the enzymatic cleavage of the gelator-drug linker is specific for the linker bonds. "Since certain enzymes are present only in specific sites within the human body–for example, at tumor sites–it is possible to use enzymes to selectively cleave bonds and thus release drugs exclusively in target areas or tissues," van Bommel says.