Abstract: A drug delivery device includes a reservoir configured to receive a fluid, a cannula in fluid communication with the reservoir, with the cannula configured to be inserted into subcutaneous tissue or muscle tissue of a patient, and a pump configured to deliver a fluid from the reservoir to the cannula. The cannula includes a bioactive agent configured to cause a tissue response to decrease a pressure required to deliver fluid from the reservoir. The tissue response can include vasodilation, vasoconstriction, increased tissue permeability, increased flow of interstitial fluid or enzymatic deterioration of extracellular matrix.