Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

Int J Nanomedicine. 2014 Jan 24:9:635-51. doi: 10.2147/IJN.S55066. eCollection 2014.


Background: Liquorice extracts demonstrate therapeutic efficacy in treating dermatitis, eczema, and psoriasis when compared with corticosteroids. In this work, nonionic surfactant vesicles (niosomes, NSVs) containing polysorbate 20 (Tween 20), cholesterol, and cholesteryl hemisuccinate at different molar concentrations were used to prepare monoammonium glycyrrhizinate (AG)-loaded NSVs. The anti-inflammatory properties of AG-loaded NSVs were investigated in murine models.

Methods: The physicochemical properties of the NSVs were characterized using dynamic light scattering. The fluidity of the lipid bilayer was evaluated by measuring the fluorescence intensity of diphenylhexatriene. The drug entrapment efficiency of AG was assessed using high-performance liquid chromatography. The physicochemical stability of the NSVs was evaluated as a function of time using dynamic light scattering combined with Turbiscan Lab Expert analysis. Serum stability was determined by incubating the NSVs with 10% v/v fetal bovine serum. The cytotoxic effects of the NSVs were investigated in human dermal fibroblasts using the Trypan blue dye exclusion assay (for cell mortality) and an MTT assay (for cell viability). Release profiles for the AG-loaded NSVs were studied in vitro using cellulose membranes. NSVs showing the most desirable physicochemical properties were selected to test for in vivo anti-inflammatory activity in murine models. The anti-inflammatory activity of the NSVs was investigated by measuring edema and nociception in mice stimulated with chemical agents.

Results: NSVs showed favorable physicochemical properties for in vitro and in vivo administration. In addition, they demonstrated long-term stability based on Turbiscan Lab Expert analysis. The membrane fluidity of the NSVs was not affected by self-assembling of the surfactants into colloidal structures. Fluorescence anisotropy was found to be independent of the molar ratios of cholesteryl hemisuccinate and/or cholesterol during preparation of the NSVs. The anti-inflammatory AG drug showed no effect on the stability of the NSVs. In vivo experiments demonstrated that AG-loaded NSVs decreased edema and nociceptive responses when compared with AG alone and empty NSVs. In vitro and in vivo results demonstrated that pH sensitive and neutral NSVs show no statistical significant difference.

Conclusion: NSVs were nontoxic and showed features favorable for potential administration in vivo. In addition, neutral NSVs showed signs of increased anti-inflammatory and antinociceptive responses when compared with AG.

Keywords: ammonium glycyrrhizinate; cytotoxicity; inflammation; niosomes; pH sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Diffusion
  • Edema / diagnosis
  • Edema / drug therapy*
  • Glycyrrhizic Acid / administration & dosage*
  • Glycyrrhizic Acid / chemistry*
  • Liposomes / chemical synthesis*
  • Male
  • Mice
  • Nanocapsules / administration & dosage*
  • Nanocapsules / chemistry*
  • Pain / diagnosis
  • Pain / drug therapy*
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • Liposomes
  • Nanocapsules
  • Glycyrrhizic Acid