On target

Prof. Helen Burt's innovations deliver drugs where the body needs them

by Hilary Thomson
Staff writer

Helen Burt's first love was always chemistry but a school tour of a hospital dispensary produced a change of heart and a lifelong passion for pharmacy.

"I thought I'd died and gone to heaven," says Burt, a professor in the Faculty of Pharmaceutical Sciences.

The trip proved to be a turning point. It inspired a 20-year academic career and an impressive record of research accomplishments.

After completing a Pharmacy undergraduate degree in England, Burt emigrated from Manchester to Canada to do her doctorate at UBC.

A faculty member since 1980, Burt's research specialty is drug delivery systems. Her expertise was recently recognized with the first Angiotech Professorship for Drug Delivery.

"Research into drug delivery looks for the most efficient way to get therapeutic agents to their target sites in the body," says Burt.

Gels, creams, tablets, patches and implants are examples of drug delivery systems.

Her interest in drug delivery started with her PhD thesis in pharmaceutics -- the study of the physical properties of drugs and delivery systems and their introduction into the body. She also studied biopharma-ceutics, looking at how drugs are absorbed into the body and how fast they are excreted.

Creating drug delivery systems for paclitaxel, the active ingredient in the widely used anti-cancer drug, Taxolreg. has been a focus for Burt since 1993 when she started collaborating with Angiotech Pharmaceuticals Inc. In 1996, she worked part-time with Angiotech as director of Research.

"There is enormous potential to be realized in biomaterials such as paclitaxel -- they form the matrix in which drugs are incorporated into the body. My dream is to build a bio-materials and drug delivery group in the faculty or between disciplines at UBC," says Burt. "The professorship will help us build those programs."

Paclitaxel is a compound derived from the Pacific Yew tree. Angiotech researchers discovered that it is a potent inhibitor of several important aspects of chronic inflammation, including cell reproduction and corresponding growth of blood vessels.

"Helen is a wonderfully innovative scientist," says Angiotech's Chair and CEO Dr. William Hunter. "We just told her what we wanted and somehow she and her research team made that a reality."

Hunter, who obtained a medical degree from UBC, saw potential applications for paclitaxel in diseases where the body mounts an immune response against itself that involves new blood vessel growth. These include rheumatoid arthritis, multiple sclerosis (MS) and psoriasis.

The obstacle was finding a way to get the drug, which is not soluble in water, absorbed and distributed in the body.

In cancer treatment paclitaxel is formulated in an oily type of vehicle that causes allergic reactions in many patients. That made it inappropriate for treatment of patients with immune diseases.

That's where Burt's expertise in drug delivery was needed.

"I could see the potential for paclitaxel right away," says Burt. "There were some technical obstacles in creating the formulations though -- we had nothing to guide us."

She devised a molecular bubble made of polymer, or biodegradable plastic, to contain the drug. The bubbles, known as micelles, have an oil-like interior which absorbs the drug and acts as a carrier but does not cause allergic reactions.

Paclitaxel's water solubility was increased 5,000 times as a result of this technology, opening the door to numerous applications.

Burt and Hunter applied for their first grant to develop the new drug delivery system in early 1993. By the end of 1994, the research had been so successful Burt's lab had expanded from one technician to 10 researchers, with Angiotech supplying $250,000 to $300,000 per year to support the work.

Last year Angiotech began clinical trials using the drug delivery system to treat MS and rheumatoid arthritis.

A debilitating, chronic inflammatory disease, rheumatoid arthritis affects one to two per cent of the world's population. The condition causes pain, swelling and destruction of multiple joints in the body and can result in damage to lungs and kidneys.

Paclitaxel may reduce symptoms of joint inflammation, bone erosion and swelling.

The same bubble technology is being tested in the treatment of MS. Also a chronic inflammatory disease, MS debilitates the neurological system and results in loss of balance, strength and vision. It affects 50,000 Canadians.

"It still amazes me that we have moved from the prototype phase to testing the applications on patients in only four years," says Burt.

She has also developed another drug delivery technology in collaboration with Angiotech, a coated stent that aids in the treatment of vascular disease. The cylindrical coated wire device is the company's best-known product.

Surgeons often use angioplasty to correct blockage of blood vessels. The procedure dilates the vessel using a balloon-tipped catheter. The deposits causing the blockage are pushed back against the walls of the vessel and a stent is sometimes inserted into the blood vessel to support the walls and hold it open.

Angioplasty and stents damage vessels, however, and can trigger a wound healing response that results in an overgrowth of tissue that narrows the vessel again. The process is known as restenosis.

Burt developed a method of coating stents with paclitaxel to inhibit the regrowth of blood vessels and tissue.

Clinical trials for the coated stents are expected to begin this year and the first coated stents could be on the market by 2001, according to Hunter.

"In 1981, I could teach the new field of drug delivery systems based on biomaterials in about three lectures," says Burt. "Now a whole year wouldn't cover it -- pharmaceutics has taken off like a rocket."

Potent new drugs that need to be delivered directly to the disease site to reduce side effects and consumer demand for controlled release products are factors that have contributed to the expansion of pharmaceutics says Burt.

Despite the exciting growth in her field, Burt says most undergraduate students find the subject difficult and dry.

One of 10 UBC faculty members who hold a certificate of teaching in higher education, Burt is determined to help her students learn pharmaceutics.

"I turn myself inside out to bring in clinical problems from real life to keep the lectures interesting," says Burt. "I also create `buzz groups' and ask the students to work with the people sitting around them to solve a problem."

Burt is also challenged and rewarded by the responsibility of supervising graduate students.

"It's deeply satisfying to see someone grow from being highly dependent on your knowledge to become an independent scientist. Seeing them surpass your own knowledge -- that's a mark of success."

Angiotech Pharmaceuticals Inc., started in 1992, is a Canadian pharmacy company that develops and commercializes new treatment for chronic inflammatory diseases.

The drug delivery technology is licensed to Angiotech through UBC's Industry Liaison Office.