Devastating blood-borne fungal infections that can be lethal for HIV/AIDS, cancer, and organ transplant patients may be treated more successfully, thanks to a new drug delivery method developed by researchers at the University of British Columbia in Vancouver.
Pharmaceutical Sciences Prof. Kishor M. Wasan has created a liquid preparation that incorporates drug molecules in fat (lipid-based formulation) so that Amphotericin B, a potent anti-fungal agent, can be taken by mouth with minimal side effects. The agent, used for about 50 years, is currently administered intravenously and has significant toxic side effects, notably severe kidney toxicity as well as serious tissue damage at the intravenous injection site.
Wasan and his research team have discovered that the oral preparation triggers a different molecular interaction than intravenous delivery. The lipid-based system attacks fungal cells only while inhibiting the drug's interaction with kidney cells -- boosting effectiveness and dramatically reducing toxicity.
The research findings will be presented today at a meeting sponsored by the American Association of Pharmaceutical Scientists in Washington, D.C. Findings will be published in July 2007 in Drug Development and Industrial Pharmacy.
Because the oral form of the drug is easier to administer and cheaper than intravenous delivery, Wasan predicts that more patients -- especially those in underserved areas and developing countries -- would have access to the medicine. He notes that Amphotericin B is also used to treat Leishmaniasis, a parasitic disease that affects an estimated two million people worldwide according to the Centers for Disease Control and Prevention (CDCP) in the U.S.
"This research was triggered by clinicians needing a way to kill these fungal infections without risking the patient's kidney," says Wasan, who is a Distinguished University Scholar and a Canadian Institutes of Health Research Chair in Drug Development. "Despite antifungal agents, treating these infections is difficult and challenges researchers to find better outcomes for the patient."
Wasan tested the drug delivery method, in animal models, against two fungal infections seen in their most severe forms in people with suppressed immune systems, such as surgical patients and those with chronic illness.
He treated Candida albicans, often seen as esophageal candidiasis, an infection prevalent in HIV/AIDS and cancer patients receiving chemotherapy, and aspergillosis, an infection caused by aspergillus fumigatis, a family of common moulds that can cause symptoms ranging from cough to brain damage. The oral formulation proved effective and minimally toxic against both infections.
A clinical study of the drug delivery system, involving 50-100 patients, is planned for later this year. A form of invasive candidiasis called candidemia is the fourth most common bloodstream infection among hospitalized patients in the U.S. A survey conducted at CDCP found that candidemia occurs in eight of every 100,000 persons per year. Persons at high risk include low-birth-weight babies and surgical patients.
Incidence of invasive aspergillosis was five-10 per 1,000, according to an analysis of medical records of 35,232 HIV-infected patients who attended outpatient clinics in 10 U.S. cities between 1990 and 1998, according to Health Canada.
Research funding for this project has been provided by the Canadian Institutes of Health Research, Canada's major agency responsible for funding health research. Composed of 13 Institutes, CIHR provides leadership and support to more than 10,000 health researchers and trainees across Canada.
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