Embodiments of the present invention provide a device for the local delivery of a substance into a natural tissue conduit in the mammalian body, having a first element capable of contacting the lumen of the conduit and a second element which overlays first element, a reservoir being formed between the first element and the second element, the interior of the reservoir being capable of fluid communication with the conduit such that a substance placed in the reservoir is delivered into the conduit. In embodiments, the first element may be fully or partially microporous or a separate intermediate microporous membrane may be provided. Also provided are methods of mixing or moving a drug within a reservoir using various mixing elements. Also provided are methods of locally delivering a substance into a natural tissue conduit in the mammalian body utilizing a device in accordance with embodiments of the present invention.