Nanotools for the Site Specific Targeting of Therapeutics
The application of nanotechnology to the miniaturization of biomedical devices (Nanomedicine) is an emerging field, anticipated over the coming years to deliver a range of new therapeutic tools that will offer the patient and physician new and more effective treatment options.Biomagnetic delivery systems have been under development since the late ‘70’s and early ‘80s.In general, historical magnetic delivery systems, while achieving tumor reduction via intra-arterial administration, have demonstrated little or no success through i.v. (systemic) administration.In order to have wide applicability to the clinic, it is nearly essential that a drug delivery platform be amenable to i.v. (systemic) administration.
In general, previous magnetic delivery systems have relied on accumulation of drug-carrier constructs at the tumor site, using external magnets to create gradients that encompassed the target site. The magnetic carriers, generally micro in size as opposed to nano-scaled, were to be held in place at the target site long enough for the drug to desorb from the carrier in the vicinity of the target site with anticipated tumor uptake. In theory, such systems were supposed to have significant advantages over non-targeting systemic administration; however, in actuality, as evidenced by the failure of clinical trials, little difference was observed between this procedure and the non-magnetic controls. The solution to site-specific drug delivery is multi-factorial, combining stealthier constructs at the nanoscale, with more powerful shaped magnetic fields, the design of which present the potential for extending magnetic saturation to deeper tumor sites.
Successful magnetic vectoring of drug-loaded magnetically responsive nanoparticles requires that (1) the magnetic vectoring device produce a magnetic field of sufficient to achieve saturation of the magnetite at a distance far enough from the magnet face to reach the volume containing the tumor, and (2) the magnet must produce a field gradient strong enough to manipulate the particles as required to enhance tumor extravasation. We have established that arrays/configurations of permanent magnets can be constructed to extend and shape the magnetic field, establishing a foundation for scaling the technology to clinical levels.
We have successfully demonstrated the tumor-specific accumulation and extravasation of magnetically responsive nanoparticles on ovarian, breast and inflammatory breast cancer models in collaborations with scientists at the M D Anderson Cancer Center (Klostergaard J, Bankson J, Yuill W, and Seeney C., “Magnetic vectoring of magnetically-responsive nanoparticles within the murine peritoneum”, J Magnetism Magnetic Materials, Vol 311, Issue 1, April 2007).
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