Oral amphotericin B: the journey from bench to market

Dolores Remedios Serrano Lopez, Katerina Lalatsa

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Abstract

Since the 1950s, amphotericin B (AmB) has been used in clinical practice to treat systemic fungal infections and leishmaniasis, a neglected parasitic disease that can be fatal if left untreated. Fungizone® (a micellar dispersion) was the “gold standard” for more than three decades but due to the safer profile of novel lipid-based medicines (AmBisome®, Abelcet® and Amphocil®), it is now used as second-line in the developed world. Lipid-based medicines possess a more favourable safety profile (mainly lower nephrotoxicity and infusion-related side effects) allowing the administration of larger doses and therefore similar efficacy with fewer administrations. However, all formulations require parenteral administration because AmB has low oral bioavailability (0.2-0.9%) due to the precipitation in aqueous media. In the last decade, strong partnerships between academia and industry has led to the development of innovative drug delivery systems able to deliver and target orally AmB in effective concentration while reducing its nephrotoxicity and infusion-related side effects. Currently, three major platform technologies (cochleates, chitosan nanoparticles and SEDDS) that are undergoing clinical trials that are discussed in this review. The pharmacokinetic and pharmacodynamic profile against visceral leishmaniasis, systemic candidiasis and aspergillosis of novel delivery systems will also be discussed.
Original languageEnglish
JournalJournal of Drug Delivery Science and Technology
Early online date13 Apr 2017
DOIs
Publication statusEarly online - 13 Apr 2017

Keywords

  • Amphotericin B
  • chitosan nanoparticles
  • self-emulsifying drug delivery systems (SEDDS)
  • oral delivery
  • cochleates
  • Ambisome®

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