Coadministration of liposomal methylglyoxal increases the activity of amphotericin B against Candida albicans in leukopoenic mice

J Drug Target. 2021 Jan;29(1):78-87. doi: 10.1080/1061186X.2020.1803333. Epub 2020 Aug 6.

Abstract

In this study, we investigated the therapeutic efficacy of a combination of liposomal amphotericin B (Lip-Amp B) and Methylglyoxal (Lip-MG) against Candida albicans in the leukopoenic mice. The antifungal efficacy of Lip-Amp B or Lip-MG or a combination of Lip-Amp B and Lip-MG was evaluated by the analysis of the survival rate and the fungal load in the treated mice. The immune-stimulatory effect of Lip-MG on macrophages was evaluated by analysing the secretion of proinflammatory cytokines. C. albicans infected mice treated at the doses of 1 and 2 mg/kg of Lip-Amp B showed 20% and 50% survival rates, respectively. Whereas the mice treated with free Amp B at the same doses died within 40 days of treatment. Interestingly, C. albicans infected mice treated with a combination of Lip-Amp B and Lip-MG had 70% survival rate on day 40 postinfection. Moreover, treatment of macrophages with Lip-MG increased their fungicidal activity and the secretion of proinflammatory cytokines, including TNF-α and IL-1β. These findings suggested that co-treatment with Lip-Amp B and Lip-MG had a synergistic effect and could be effective against C. albicans in immunocompromised subjects.

Keywords: Methylglyoxal; leukopenia; liposomes; macrophages; systemic candidiasis.

MeSH terms

  • Amphotericin B / administration & dosage*
  • Animals
  • Antifungal Agents / administration & dosage*
  • Candida albicans / drug effects*
  • Candida albicans / physiology
  • Drug Therapy, Combination
  • Female
  • Leukopenia / drug therapy*
  • Leukopenia / immunology
  • Leukopenia / pathology
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Pyruvaldehyde / administration & dosage*

Substances

  • Antifungal Agents
  • Liposomes
  • liposomal amphotericin B
  • Pyruvaldehyde
  • Amphotericin B