Title:  Implantable system with drug-eluting cells for on-demand local drug delivery

United States Patent:  6,206,914

Assignee:  Medtronic, Inc. (Minneapolis, MN)

Filed:  August 31, 1998

An implantable system that includes a carrier and eukaryotic cells, which produce and release a therapeutic agent, and a stimulating element for stimulating the release of the therapeutic agent. The system can also include a sensing element for monitoring a physiological condition and triggering the stimulating element to stimulate the delivery device to release the therapeutic agent. Alternatively, the patient in which the system is implanted can activate the stimulating element to release the therapeutic agent.

SUMMARY OF THE INVENTION

The present invention provides implantable systems that include delivery devices having a carrier and eukaryotic cells associated therewith, optionally within a containment vehicle. Such cells are capable of producing at least one therapeutic agent (i.e., drug), which is released from the delivery device upon the application of a stimulus (e.g., electrical stimulus) for on-demand (i.e., when needed) localized treatment of conditions such as coronary artery disease or cerebral is vascular occlusion, for example. The cells are referred to herein as "drug-eluting" cells.

Release of the therapeutic agent from the delivery device is stimulated by a variety of methods, including electrical stimulation, which can be used to create an electrical field or mechanical stimulus, for example. This can be accomplished by direct action on the cells, such as by stimulating the cellular membrane to release the cellular products contained therein. Alternatively, this can be accomplished by activating the cellular products such that upon release they will function as therapeutic agents. This can also be accomplished by stimulating a microscopic containment vehicle that contains the cells, such as by stimulating a synthetic membrane of the containment vehicle, to release the cells and/or their cellular products.

Thus, an object of the present invention is to provide a system and method for the treatment (including prevention) of coronary artery disease, for example, by producing and delivering locally a therapeutic agent, such as an anticoagulant. Significantly, the local dosage can be controlled and provided on demand without worrying about the systemic effects. Furthermore, the local dosage can be administered prior to significant physiological damage occurs to the patient.

In a preferred embodiment, the present invention provides an implantable system that includes: a delivery device comprising a carrier for carrying eukaryotic cells that produce at least one therapeutic agent; a stimulating element for stimulating the release of the therapeutic agent from the delivery device; and a sensing element for monitoring at least one physiological property of a patient in which the system is implanted and communicating with the stimulating element to stimulate the release of the therapeutic agent from the delivery device.

In another embodiment, an implantable system includes a delivery device comprising an intraluminal stent, which includes a lumen-wall contacting surface, a lumen-exposed surface, a first polymer composition covering at least a portion of the stent (preferably, at least a portion of the lumen-exposed and the lumen-wall contacting surfaces), and endothelial cells associated with the first polymer composition covering, wherein the endothelial cells produce at least one therapeutic agent. The implantable system further includes an electrical stimulating element for stimulating the release of the therapeutic agent from the delivery device, and a sensing element for monitoring at least one physiological property of a patient in which the system is implanted and communicating with the electrical stimulating element to stimulate the release of the therapeutic agent from the delivery device.

The present invention also provides a method of local delivery (as opposed to systemic delivery) of a therapeutic agent. The method involves simply implanting an implantable system described above. Once implanted into a patient, the therapeutic agent is released from the delivery device when the sensing element detects a predetermined level of a physiological property (e.g., a certain pH or level of blood flow or blood gases) and communicating with the stimulating element to trigger the release.

A method of making an implantable system for local delivery of a therapeutic agent is also included within the scope of the present invention. The method includes: providing a delivery device comprising a carrier and eukaryotic cells associated therewith that produce at least one therapeutic agent; providing a stimulating element for stimulating the release of the therapeutic agent from the delivery device; providing a sensing element for monitoring at least one physiological property of a patient in which the system is implanted; and connecting the stimulating element and sensing element such that they communicate with each other to stimulate the release of the therapeutic agent from the delivery device when implanted in the body of a patient and the sensing element detects a predetermined level of a physiological property. Preferably, the step of providing a delivery device includes: providing a carrier; isolating eukaryotic cells from a patient; culturing the eukaryotic cells; delivering nucleic acid of a desired therapeutic agent to the eukaryotic cells to form genetically engineered eukaryotic cells; and contacting the carrier with the genetically engineered eukaryotic cells.

In an alternative embodiment, the present invention provides implantable systems as described above without the sensing element. In such systems, the patient in which the system is implanted activates the stimulating element when desired (i.e., on demand). Typically, this occurs when the patient detects a change in a physiological condition (e.g., angina) and communicates with the electrical stimulating element to trigger release of the therapeutic agent. The patient can communicate with the electrical stimulating element to activate it using radio frequency, infrared, or acoustic pulses.

Claim 1 of 37 Claims

What is claimed is:

1. An implantable system comprising:

(a) a delivery device comprising a carrier and eukaryotic cells that produce at least one therapeutic agent;

(b) a stimulating element operatively coupled to the delivery device for stimulating the release of the therapeutic agent from the delivery device; and

(c) a sensing element for monitoring at least one physiological property of a patient in which the system is implanted and communicating with the stimulating element to stimulate the release of the therapeutic agent from the delivery device.

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