Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 42, Issue -, Pages 75-83Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jddst.2017.04.017
Keywords
Amphotericin B; Ambisome((R)); Oral delivery; Cochleates; Self-emulsifying drug delivery systems (SEDDS); Chitosan nanoparticles
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Funding
- Sir Halley Stewart Trust [127]
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Since the 1950s, amphotericin B (AmB) has been used in the clinical practice to treat systemic fungal infections and leishmaniasis, a neglected parasitic disease that can be fatal if left untreated. Fungizone((R)) (a micellar dispersion) was the gold standard for more than three decades but due to the safer profile of novel lipid-based medicines (AmBisome((R)), Abelcet((R)) and Amphocil((R))), 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 of drug 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 concentrations while reducing its nephrotoxicity and infusion-related side effects. Currently, three major platform technologies (cochleates, chitosan nanoparticles and SEDDS) that are undergoing clinical trials are discussed in this review. The pharmacokinetic and pharmacodynamic profile against visceral leishmaniasis, systemic candidiasis and aspergillosis of novel delivery systems will be discussed. (C) 2017 Elsevier B.V. All rights reserved.
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