Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance

Amphotericin B is an effective polyene antifungal considered as a "gold standard" in the management of fungal infections. Currently, it is administered mainly by IV due to poor aqueous solubility, which precludes its delivery orally. Paradoxically, IV administration is akin to side effects that have not been fully eliminated even with more recent IV formulations. Thus, the need for alternative formulations/route of administration for amphotericin B remains crucial. The oral route offers the possibility of delivering amphotericin B systemically and with diminished side effects; however, enterocyte permeation remains a constraint. Cellular phagocytosis of submicron particles can be used to courier encapsulated drugs. In this regard, nanoparticulate delivery systems have received much attention in the past decade. This review examines the trajectory of orally delivered amphotericin B and discusses key physical factors of nanoformulations that impact bioavailability. The review also explores obstacles that remain and gives a window into the possibility of realizing an oral nanoformulation of amphotericin B in the near future.