Enzyme Prodrug Therapy Engineered into Biomaterials

摘要

In this work, enzyme-prodrug therapy (EPT) is engineered into hydrogel biomaterials to achieve localized synthesis of the drugs and their delivery to the adhering cells. The use of EPT in the context of drug delivery mediated by biomaterials significantly empowers the latter in that the same hydrogel is used to successfully synthesize several drugs with dissimilar structures and therapeutic effects. The concentration of the synthesized drugs is conveniently controlled by the concentration of the administered prodrugs. Using prodrugs for two therapeutic agents allows their synthesis and delivery with independent control over the concentration and the time of administration of each of the drugs. Using these tools, sequential delivery of drugs for anti-inflammatory and anti-proliferative activity is accomplished whereby the synthesis of drugs is mediated by the same enzyme-functionalized hydrogel. The use of EPT to perform combination therapy mediated by an implantable biomaterial is also reported. Taken together, these results contribute significantly to the development of flexible and highly powerful tools of substrate-mediated drug delivery with applications in the design of therapeutic implants and tissue engineering.