Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Development of an Oral Amphotericin B Formulation as an Alternative Approach to Parenteral Amphotericin B Administration in the Treatment of Blood-Borne Fungal Infections

Author(s): Kishor M. Wasan*

Volume 26, Issue 14, 2020

Page: [1521 - 1523] Pages: 3

DOI: 10.2174/1381612826666200311130812

Price: $65

Abstract

In the Fall of 1999, we presented at medical “Grand Rounds” to a number of Infectious Diseases physicians at Vancouver General Hospital about the co-administration of several antifungal compounds in the treatment of blood-borne fungal infections to patients who were immunocompromised (i.e. cancer patients, patients waiting organ transplantation, HIV/AIDs patients, etc.). During the presentation, a physician from the back of the room called out “can you develop an oral formulation of amphotericin B which could be effective and not have the side-effects associated with the parenteral formulations of the drug”. The physician stated that an oral formulation would be a big step forward, improving patient compliance, helping in pre-treatment without admitting patients to the hospital prior to organ transplantation and it would be cost-effective.

Initially, I responded to the physician, that it would not be possible to develop an oral amphotericin B formulation that could be absorbed from the gastrointestinal (GI) tract in a high enough concentration to be effective in treating blood-borne fungal infections and yet remains non-toxic due to the physical chemical properties of the drug.

However, as I travelled back to my lab from the meeting, it struck me that our understanding of how lipids had been processed and orally absorbed from the GI had advanced to the point the maybe incorporating amphotericin B into such lipids might work.

Within several years, our laboratory was able to develop a novel oral amphotericin B formulation that was indeed effective in treating systemic fungal infections without the side-effects associated with the drug in a variety of fungal animal models.

Keywords: Oral amphotericin B formulation, drug delivery, systemic fungal infections, parasitic infections, Phase I Clinical Trials, HIV/AIDS.

« Previous Next »
[1]
Cuddihy G, Wasan EK, Di Y, Wasan KM. The development of oral amphotericin B to treat systemic fungal and parasitic infections: has the myth been finally realized? Pharmaceutics 2019; 11(3) E99
[http://dx.doi.org/10.3390/pharmaceutics11030099] [PMID: 30813569]
[2]
Leon CG, Lee J, Bartlett K, et al. In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009 and iCo-010) against Candida albicans, human monocytic and kidney cell lines. Lipids Health Dis 2011; 10: 144.
[http://dx.doi.org/10.1186/1476-511X-10-144] [PMID: 21854638]
[3]
Gershkovich P, Wasan EK, Lin M, et al. Pharmacokinetics and biodistribution of amphotericin B in rats following oral administration in a novel lipid-based formulation. J Antimicrob Chemother 2009; 64(1): 101-8.
[http://dx.doi.org/10.1093/jac/dkp140] [PMID: 19398459]
[4]
Wasan EK, Bartlett K, Gershkovich P, et al. Development and characterization of oral lipid-based amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans. Int J Pharm 2009; 372(1-2): 76-84.
[http://dx.doi.org/10.1016/j.ijpharm.2009.01.003] [PMID: 19236839]
[5]
Ibrahim F, Gershkovich P, Sivak O, Wasan EK, Bartlett K, Wasan KM. Efficacy and toxicity of a tropically stable lipid-based formulation of amphotericin B (iCo-010) in a rat model of invasive candidiasis. Int J Pharm 2012; 436(1-2): 318-23.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.062] [PMID: 22772485]
[6]
Wasan KM, Sivak O, Bartlett K, Wasan EK, Gershkovich P. Novel oral amphotericin B formulation (iCo-010) remains highly effective against murine systemic candidiasis following exposure to tropical temperature. Drug Dev Ind Pharm 2015; 41(9): 1425-30.
[http://dx.doi.org/10.3109/03639045.2014.954587] [PMID: 25170660]
[7]
Ibrahim F, Sivak O, Wasan EK, Bartlett K, Wasan KM. Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis. Lipids Health Dis 2013; 12: 158.
[http://dx.doi.org/10.1186/1476-511X-12-158] [PMID: 24164705]
[8]
Ibrahim F, Gershkovich P, Sivak O, Wasan EK, Wasan KM. Pharmacokinetics and tissue distribution of amphotericin B following oral administration of three lipid-based formulations to rats. Drug Dev Ind Pharm 2013; 39(9): 1277-83.
[http://dx.doi.org/10.3109/03639045.2012.719908] [PMID: 22989082]
[9]
Ibrahim F, Gershkovich P, Sivak O, Wasan EK, Wasan KM. Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Eur J Pharm Sci 2012; 46(5): 323-8.
[http://dx.doi.org/10.1016/j.ejps.2012.02.008] [PMID: 22369857]
[10]
Sivak O, Gershkovich P, Lin M, et al. Tropically stable novel oral lipid formulation of amphotericin B (iCo-010): biodistribution and toxicity in a mouse model. Lipids Health Dis 2011; 10: 135.
[http://dx.doi.org/10.1186/1476-511X-10-135] [PMID: 21824435]
[11]
Wasan EK, Gershkovich P, Zhao J, et al. A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. PLoS Negl Trop Dis 2010; 4(12) e913
[http://dx.doi.org/10.1371/journal.pntd.0000913] [PMID: 21151883]
[12]
Gershkovich P, Sivak O, Wasan EK, et al. Biodistribution and tissue toxicity of amphotericin B in mice following multiple dose administration of a novel oral lipid-based formulation (iCo-009). J Antimicrob Chemother 2010; 65(12): 2610-3.
[http://dx.doi.org/10.1093/jac/dkq358] [PMID: 20861140]
[13]
Wasan KM, Wasan EK, Gershkovich P, et al. Highly effective oral amphotericin B formulation against murine visceral leishmaniasis. J Infect Dis 2009; 200(3): 357-60.
[http://dx.doi.org/10.1086/600105] [PMID: 19545212]
[14]
Thornton SJ, Wasan KM. The reformulation of amphotericin B for oral administration to treat systemic fungal infections and visceral leishmaniasis. Expert Opin Drug Deliv 2009; 6(3): 271-84.
[http://dx.doi.org/10.1517/17425240902802861] [PMID: 19327044]
[15]
Sachs-Barrable K, Lee SD, Wasan EK, Thornton SJ, Wasan KM. Enhancing drug absorption using lipids: a case study presenting the development and pharmacological evaluation of a novel lipid-based oral amphotericin B formulation for the treatment of systemic fungal infections. Adv Drug Deliv Rev 2008; 60(6): 692-701.
[http://dx.doi.org/10.1016/j.addr.2007.08.042] [PMID: 18053611]
[16]
Risovic V, Rosland M, Sivak O, Wasan KM, Bartlett K. Assessing the antifungal activity of a new oral lipid-based amphotericin B formulation following administration to rats infected with Aspergillus fumigatus. Drug Dev Ind Pharm 2007; 33(7): 703-7.
[http://dx.doi.org/10.1080/03639040601077349] [PMID: 17654018]
[17]
Available at. http://icotherapeutics.com/2018/07/16/ico-therapeutics-announces-positive-secondary-endpoint-and-advancement-into-later-stage-clinical-trials-phase-1-oral-amphotericin-b/
[18]
Available at. https://www.newsfilecorp.com/release/35503/iCo-Therapeutics-Announces-Positive-Clinical-Outcome-Primary-Endpoint-Met-in-Phase-1-Oral-Amphotericin-B-Study
[19]
Available at. http://icotherapeutics.com/2018/09/06/ico-therapeutics-announces-additional-positive-pharmacokinetic-results-and-presentation-at-global-investment-conference/
[20]
Fernández-García R, de Pablo E, Ballesteros MP, Serrano DR. Unmet clinical needs in the treatment of systemic fungal infections: The role of amphotericin B and drug targeting. Int J Pharm 2017; 525(1): 139-48.
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.013] [PMID: 28400291]
[21]
Serrano DR, Lalatsa A. Oral amphotericin B: The journey from bench to market. J Drug Deliv Sci Technol 2017; 42: 75-83.
[http://dx.doi.org/10.1016/j.jddst.2017.04.017]
[22]
Ling Tan JS, Roberts CJ, Billa N. Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B. Pharm Dev Technol 2018; 26: 1-9.
[http://dx.doi.org/10.1080/10837450.2018.1515225] [PMID: 30132723]
[23]
Radwan MA, AlQuadeib BT, Šiller L, Wright MC, Horrocks B. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats. Drug Deliv 2017; 24(1): 40-50.
[http://dx.doi.org/10.1080/10717544.2016.1228715] [PMID: 28155565]
[24]
Chaudhari MB, Desai PP, Patel PA, Patravale VB. Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module. Drug Deliv Transl Res 2016; 6(4): 354-64.
[http://dx.doi.org/10.1007/s13346-015-0267-6] [PMID: 26712123]
[25]
Chen YC, Su CY, Jhan HJ, Ho HO, Sheu MT. Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles. Int J Nanomedicine 2015; 10: 7265-74.
[http://dx.doi.org/10.2147/IJN.S95194] [PMID: 26664117]
[26]
Mohamed HA, Radwan RR, Raafat AI, Ali AE. Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study. Drug Deliv Transl Res 2018; 8(1): 191-203.
[http://dx.doi.org/10.1007/s13346-017-0452-x] [PMID: 29280061]

Rights & Permissions Print Cite
Article Metrics
21
2
World Health Day
© 2024 Bentham Science Publishers | Privacy Policy