Magnetically-controllable delivery system for therapeutic agents

Abstract

A magnetic delivery system for delivering a magnetizable particle to a location in a body, the device includes a magnetizable object implanted in the body, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting the magnetizable particle and an external source of a magnetic field capable of (i) magnetizing the magnetizable particle and (ii) increasing a degree of magnetization of the magnetizable object and thereby creating the magnetic gradient. A drug delivery system including the magnetic delivery system and a magnetizable particle associated with a therapeutic agent and / or a cell. A cell delivery system based on the magnetic delivery system and a magnetizable particle associated with a cell. A method of using the magnetic delivery system for delivery of a therapeutic agent and / or a cell to a targeted location in a body.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of the PCT application titled “MAGNETICALLY CONTROLLABLE DRUG AND GENE DELIVERY STENTS” having the application Ser. No. PCT / US2004 / 011861 and filed on Apr. 16, 2004, which claims the benefit of provisional Application No. 60 / 463,505, filed on Apr. 16, 2003, titled MAGNETIZABLE IMPLANTS AND METHODS FOR TARGETED DELIVERY OF MAGNETICALLY SUSCEPTIBLE THERAPEUTIC AGENTS which are incorporated herein in their entireties. [0002] This application claims the benefit of provisional Application No. 60 / 680,833, filed on May 13, 2005, titled METHOD OF MAGNETIC DELIVERY OF CELLS AND BIOLOGICS, which is incorporated herein in its entirety.SPECIFICATION BACKGROUND OF THE INVENTION [0003] 1. Field of Invention [0004] The present invention relates to magnetically controllable delivery systems and methods of using thereof to attract and deliver therapeutic agents attached to, or encapsulated within, magnetic part...

AI Technical Summary

Benefits of technology

[0028] In certain embodiments, the magnetization of at least one of the magnetizable object and the magnetizable particle is increased in the presence of the external magnetic field.

[0029] Further provided is a method of using the magnetic delivery system for delivery of a therapeutic agent, the method comprising providing the external source of the magnetic field, implanting the magnetizable object in the body, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting a magnetizable particle comprising a therapeutic agent, and providing an external magnetic field by initializing the external source and thereby (i) magnetizing the magnetizable particle and (ii) increasing the degree of magnetization the magnetizable object and thereby creating the magnetic gradient for attracting and advancing the magnetizable particle toward the magnetizable object.

[0032] In a preferred embodiment, the invention provides a magnetizable implant, preferably a stent, for targeting of magnetic therapeutic agents to a selected site of implantation of the magnetizable implant in a subject through creation of a high field magnetic gradient as well as creation of a relatively uniform magnetic field for magnetizing the magnetic therapeutic agents. In the present invention, two magnetic fields are independently produced in order to improve capture efficiency and uniformity of captured therapeutic agent as a coating on the implant, as well as to allow for miniaturization of the implant.

[0034] Optimization of the segments (i.e., features) of the implant to produce strong magnetic field gradients reduces the penetration of the magnetic field into the surrounding tissue. Thus, in the present invention, in order to magnetize the magnetic carrier of a therapeutic agent to saturation, a second relatively uniform magnetic source is used which can penetrate deep into the selected delivery site and / or tissue of interest. In one embodiment, this second relatively uniform source is applied externally through use of large electromagnets. In another embodiment, the second relatively uniform magnetic source is implanted internally. In this embodiment, the second relatively uniform magnetic source may be separate from the implant or part of the implant that also creates strong magnetic field gradients.

Problems solved by technology

Many drugs developed by the pharmaceutical industry have shown remarkable success during in vitro testing and animal trials, but have yielded undesirable results in clinical trials due to systemic toxicity of the drug to the body.

However, known drug delivery vehicles are not capable of local delivery of high concentrations of drugs by minimally invasive techniques.

However, in-stent restenosis (the re-closing of the vessel) remains a major limitation, particularly in coronary stenting.

However, neo-intimal growth or proliferation is still a problem.

However, clinical success has been limited (Garas et al.

Problems with these technologies, however, include the inflammatory response generated due to large polymer concentrations, the inability to deliver effective concentrations, one-time dosage limitations, and, in the case of the biodegradable stent, mechanical compromise.

An additional concern with the polymer-coated drug-eluting stents is limitation of the growth of the cell layer necessary to cover the stent and prevent the bare metal from coming in long contact with the blood, thereby leading to clot formation (Schwartz et al.

The main disadvantage of this approach is that externally generated magnetic fields apply relatively small and insufficiently local forces on micron and nano-scale magnetic particles, and thus these methods have limited applications.

Gordon does not disclose optimizing the surface of the implant for providing a stronger magnetic field gradient.

Single source capture methods, however, are at odds with the underlying physics of magnetic particle capture, which depends on the simultaneous imposition of very strong far-reaching magnetic fields and strong spatial magnetic field gradients.

Thus, the ability to simultaneously produce far-penetrating magnetic fields that have strong magnetic filed gradients is very difficult to accomplish with a single source.

For this reason, Chen teaches use of relatively large electromagnets implanted in tissue beds to attract magnetic fluid circulating within the blood vessels that are relatively far away, which is a less effective method for capturing magnetic carriers.

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