Friday, May 17, 2013
“Development and Evaluation of a Novel Oral Amphotericin B Formulation for the Treatment of Systemic Fungal Infections and Drug-Resistant Visceral Leishmaniasis (VL)”
KISHOR M.WASAN, R.Ph., Ph.D., FAAPS, FCAHS
Our laboratory has made significant strides toward the development of a lipid-based amphotericin B formulation for oral administration. Initial data from both cell lines and in vivo research indicate that it is highly efficacious and exhibits low toxicity within the dosage range required in treating diseases such as systemic fungal infections and leishmaniasis.
Each year in the Indian subcontinent alone, over 500,000 individuals play host to Leishmania donovani, an insidious parasite that invades macrophages, rapidly infiltrates the vital organs and ultimately leads to severe infection of the visceral reticuloendothelial system. Visceral leishmaniasis, also known as Kala-azar, is most prevalent in the weak and the young within a population. Left untreated, almost all infected individuals will die. The therapeutic arsenal against Leishmania is limited to a small number of parenterally administered agents, with daily injections of pentavalent antimony compound for 28 days being the usual course of action. Due to increasing resistance, antimonial drugs can no longer be used in many areas, including northeastern India where the incidence of Kala-azar is highest.
Amphotericin B is the current secondary treatment of choice against leishmaniasis and has a 97% cure rate with no reported resistance. However, therapy with the first-generation formulation (FungizoneR) involves IV administration over a period of 30 to 40 days and is associated with infusion and drug-related side-effects (infection of the indwelling catheter, patient chills and shaking due to RBC haemolysis, dose-dependent renal toxicity, fever, bone pain, thrombophlebitis).
Although lipid-based second-generation formulations exist (AbelcetR and AmBisomeR), which require a shorter course of therapy (3-5 days), are highly effective and exhibit lower toxicity when compared to FungizoneR, the cost of these formulations is a barrier to widespread use. Due to the difficult route of drug administration, toxicity issues and cost, amphotericin B is failing to reach the infected population and mortality rates continue to rise.
The development of an inexpensive, safe and effective oral treatment is paramount in order to address both early and late stages of this deadly disease and drug-resistant forms of VL. This talk will highlight our current findings and future goals.
Dr. Kishor M. Wasan has been a faculty member at the University of British Columbia for 18 years, during which time he has published over 200 peer-reviewed articles and 250 abstracts in the area of lipid-based drug delivery and lipoprotein-drug interactions. His work was recently highlighted in the January 2008 Issue of Nature Reviews, Drug Discovery. Dr. Wasan did his undergraduate degree in Pharmacy at the University of Texas at Austin and his Ph.D. at the University of Texas Medical Center in Houston Texas at MD Anderson Cancer Center in Cellular and Molecular Pharmacology. After completing a postdoctoral fellowship in Cell Biology at the Cleveland Clinic, Dr. Wasan joined the Faculty of Pharmaceutical Sciences at UBC.
Dr. Wasan was one of the recipients of the 1993 American Association of Pharmaceutical Scientists (AAPS) Graduate Student Awards for Excellence in Graduate Research in Drug Delivery, the 2001 AAPS New Investigator Award/Grant in Pharmaceutics and Pharmaceutics Technologies, the 2002 Association of Faculties of Pharmacy of Canada New Investigator Research Award and recently was named an AAPS fellow in 2006. In addition, Dr. Wasan was awarded a Canadian Institutes of Health Research University-Industry Research Chair in Pharmaceutical Development (2003-2008), was named a University Distinguished Scholar in April 2004, received the 2007 AAPS Award for Outstanding Research in Lipid-Based Drug Delivery, and received the 2008 AFPC-Pfizer Research Career Award.
In April 2009 Dr. Wasan was named CIHR/iCo Therapeutics Research Chair in Drug Delivery for Neglected Global Diseases and on September 30, 2010 Dr. Wasan was named a Fellow of the Canadian Academy of Health Sciences. In May 2011, Dr. Wasan received the Canadian Society of Pharmaceutical Sciences Leadership award for outstanding contributions to Pharmaceutical Sciences in Canada. Currently Dr. Wasan's research is supported by grants from The Canadian Institutes of Health Research (CIHR), The Natural Sciences and Engineering Research Council of Canada (NSERC) and several Pharmaceutical companies.