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Liposome-mediated delivery of iminosugars enhances efficacy against dengue virus in vivo.

Miller, JL ; Lachica, R ; et al.
In: Antimicrobial agents and chemotherapy, Jg. 56 (2012-12-01), Heft 12, S. 6379-86
Online academicJournal
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A key challenge faced by promising antiviral drugs, such as iminosugars, is in vivo delivery to achieve effective levels of drug without toxicity. Four iminosugars, all deoxynojirimycin (DNJ) derivatives-N-butyl DNJ (NB-DNJ), N-nonyl DNJ, N-(9-methoxynonyl) DNJ, and N-(6'-[4″-azido-2″-nitrophenylamino]hexyl)-1-DNJ (NAP-DNJ)-potently inhibited both the percentage of cells infected with dengue virus and release of infectious virus from primary human monocyte-derived macrophages, demonstrating their efficacy in primary cells. In a lethal antibody-dependent enhancement mouse model of dengue pathogenesis, free NB-DNJ significantly enhanced survival and lowered viral load in organs and serum. Liposome-mediated delivery of NB-DNJ, in comparison with free NB-DNJ, resulted in a 3-log(10) reduction in the dose of drug sufficient to enhance animal survival. The optimizing of the effective dose in this way could liberate the therapeutic potential of many cytotoxic antivirals against both dengue virus and a wide array of other viruses.

Titel:
Liposome-mediated delivery of iminosugars enhances efficacy against dengue virus in vivo.
Autor/in / Beteiligte Person: Miller, JL ; Lachica, R ; Sayce, AC ; Williams, JP ; Bapat, M ; Dwek, R ; Beatty, PR ; Harris, E ; Zitzmann, N
Link:
Zeitschrift: Antimicrobial agents and chemotherapy, Jg. 56 (2012-12-01), Heft 12, S. 6379-86
Veröffentlichung: Washington, American Society for Microbiology, 2012
Medientyp: academicJournal
ISSN: 1098-6596 (electronic)
DOI: 10.1128/AAC.01554-12
Schlagwort:
  • 1-Deoxynojirimycin administration & dosage
  • 1-Deoxynojirimycin therapeutic use
  • Animals
  • Cell Survival drug effects
  • Dengue virology
  • Drug Carriers
  • Drug Delivery Systems
  • Gene Dosage
  • Humans
  • In Vitro Techniques
  • Liposomes
  • Macrophages drug effects
  • Macrophages microbiology
  • Mice
  • RNA, Viral biosynthesis
  • RNA, Viral genetics
  • Real-Time Polymerase Chain Reaction
  • Antiviral Agents administration & dosage
  • Antiviral Agents therapeutic use
  • Dengue drug therapy
  • Dengue Virus drug effects
  • Imino Sugars administration & dosage
  • Imino Sugars therapeutic use
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article; Research Support, Non-U.S. Gov't
  • Language: English
  • [Antimicrob Agents Chemother] 2012 Dec; Vol. 56 (12), pp. 6379-86. <i>Date of Electronic Publication: </i>2012 Oct 15.
  • MeSH Terms: Antiviral Agents / *administration & dosage ; Antiviral Agents / *therapeutic use ; Dengue / *drug therapy ; Dengue Virus / *drug effects ; Imino Sugars / *administration & dosage ; Imino Sugars / *therapeutic use ; 1-Deoxynojirimycin / administration & dosage ; 1-Deoxynojirimycin / therapeutic use ; Animals ; Cell Survival / drug effects ; Dengue / virology ; Drug Carriers ; Drug Delivery Systems ; Gene Dosage ; Humans ; In Vitro Techniques ; Liposomes ; Macrophages / drug effects ; Macrophages / microbiology ; Mice ; RNA, Viral / biosynthesis ; RNA, Viral / genetics ; Real-Time Polymerase Chain Reaction
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  • Substance Nomenclature: 0 (Antiviral Agents) ; 0 (Drug Carriers) ; 0 (Imino Sugars) ; 0 (Liposomes) ; 0 (RNA, Viral) ; 19130-96-2 (1-Deoxynojirimycin)
  • Entry Date(s): Date Created: 20121017 Date Completed: 20130228 Latest Revision: 20211021
  • Update Code: 20240513
  • PubMed Central ID: PMC3497178

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