Our research aims at the development of better targeted drugs for cancer therapy. To do this, we develop radioactive pharmaceuticals (= radiopharmaceuticals), determine their microdosimetry, and then deliver them to different organs and tumours. A particularly fascinating approach to deliver pharmaceuticals that we investigate is magnetic drug targeting.
Radiopharmaceuticals
Radioactive drugs can be used for many therapeutic purposes such as cancer treatment or scar prevention. Radiopharmaceuticals, the general name for radiolabeled diagnostic and therapeutic agents, can take many different shapes including particles sized from tens of nanometers (= nanospheres) up to about 100 micrometers (= microspheres), viscous solutions and micellar/liposomal suspensions, sheets, and even metal implants such as stents (metal or plastic coils) or foils. Our lab is interested in preparing radioactively labelled drug delivery vehicles and using them to kill tumours and prevent their reoccurrence. The images to the right show a few of the radiopharmaceuticals we recently prepared and tested, both in vitro and in vivo.
The main radioactive isotopes we are currently investigating are the beta-emitters rhenium-188 (Re-188), yttrium-90 (Y-90), and their diagnostic counterparts technetium-99m (Tc-99m) and indium-111 (In-111). Earlier, we used other isotopes such as iodine-125 (I-125), iodine-131 (I-131), palladium-103 (Pd-103) and iridium-192 (Ir-192). Future research will also include PET-isotopes due to the close affiliation of the Faculty of Pharmaceutical Sciences with researchers from TRIUMF, the largest Canadian cyclotron. TRIUMF is located only a few minutes from the Pharmaceutical Sciences building and is able to produce many novel and desirable PET-isotopes.
Magnetic Microspheres
The main problem of cancer therapy is not the lack of efficient drugs, but that these drugs are very difficult to concentrate in the tumour tissue without leading to toxic effects on neighbouring organs and tissues. One method to accomplish this is by magnetic drug delivery with particulate carriers, a very efficient method of delivering a drug to a localized disease site. The figure to the left highlights the concept of magnetic targeting by comparing it with systemic drug delivery. In magnetic targeting, a drug or therapeutic radioisotope is bound to a magnetic compound, injected into a patient’s blood stream, and then stopped with a powerful magnetic field in the target area. Depending on the type of drug, it is then slowly released from the magnetic carriers (e.g., release of chemotherapeutic drugs from magnetic microspheres) or confers a local effect (e.g., irradiation from radioactive microspheres; hyperthermia with magnetic nanoparticles). Small amounts of drug targeted magnetically to localized disease sites can thus possibly replace large amounts of freely circulating drug and reach effective and up to several-fold increased localized drug levels.
In our lab, we are currently investigating new ways of preparing uniform magnetic microspheres with a diameter of 1.0 µm, made from biodegradable materials and appropriate for human use. We are also interested in evaluating the toxicity of the whole microspheres and the small magnetic nanoparticles which give them their magnetic properties. These investigations are based on cell survival experiments and confocal microscopy investigations over time in cell cultures.
Drug Delivery with Microneedles
In collaboration with Prof. Boris Stoeber, Departments of Mechanical Engineering & Electrical and Computer Engineering at UBC, we are working on the use of silicon and polymer-based microneedles. Typically 150 µm high, they allow for the penetration of the skin without touching the (deeper) nerve endings, and thus permit pain-free drug delivery to areas in the skin. From there, the drug can either be delivered to the blood capillaries, or then work locally, as for example needed in the case of vaccinations.