Abstract
Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations.
Highlights
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
KMW considered it extremely challenging to develop a bioavailable formulation of amphotericin B that would achieve the tissue concentrations required to have a pharmacological effect and ameliorating the dose-dependent nephrotoxicity associated with the drug
Generalizations can be made with regard to the the pharmacophore of this molecule: The positively charged amino group is required for activity; pharmacophore of this molecule: for Theactivity; positively charged amino group is requiredcharged, for activity; the the polyene subunit is important if the carboxyl group is negatively it leads polyene subunit is important for activity; if the carboxyl group is negatively charged, it leads to to decreased selectivity for ergosterol over cholesterol; and N-aminoacylation leads to decreased selectivity for ergosterol over cholesterol; and N-aminoacylation leads to improved selectivity [1]
Summary
One of the authors (KMW) was presenting grand rounds to the infectious disease group at Vancouver General Hospital, discussing combination therapies to treat systemic fungal infections, those patients who were about to go through organ transplantation. An infectious disease physician asked if it was possible to develop an oral formulation of amphotericin B to treat patients. This physician commented that if an oral formulation could be developed, it would be widely used, because it would have the potential to overcome many of the limitations of intravenous administration. These limitations include affordability, accessibility, and the well-known systemic toxicities associated with amphotericin B. As KMW thought about it, it became clear that with a growing understanding of dietary and excipient lipid processing in the gastrointestinal tract (GIT) as well as associated new drug delivery technologies, it could be possible to develop an efficacious oral formulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
