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

Abstract

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(R) 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 anti-nociceptive responses when compared with AG

Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

“…Furthermore, zymosan-induced paw edema is COX-2-dependent since it is significantly reduced in COX-2 −/− mice [45]. In this context, previous studies demonstrated that AG was able to reduce paw [15,16] or ear [16] edema formation and these effects were observed from 1 to 5 h after its administration [46]. After carrageenan injection in mouse paw, TNF-α, IL-6, iNOS, and COX-2 mRNA expressions increased and AG treatment (150 mg/kg, i.p.)…”

Long-Lasting, Antinociceptive Effects of pH-Sensitive Niosomes Loaded with Ibuprofen in Acute and Chronic Models of Pain

“…The increase in drug activity when released by niosomes could be explained by the capability of niosomes to transport lipophilic drugs, in this case Ibuprofen, across tissue membranes. This facilitates drug diffusion around the site of application and consequently improves efficacy [13,22].…”

“…Niosomes based on a polysorbate-20 glycine derivative (Tw20Gly) were prepared by the thin film evaporation method at different Ibuprofen loading concentrations (Table 1) and purified by glass chromatography, as previously described [21,22]. A Nano ZS90 Dynamic light scattering LS (Malvern Instruments Ltd., Malvern, UK) at a scattering angle of 90.0° and a LS50B spectrofluorometer (PerkinElmer, MA, USA), were both employed for the physico-chemical characterization of vesicles (hydrodimanic diameter, size distribution, zeta potential, bilayer properties, stability, and in vitro release studies) [21].…”

“…In this context, niosomes with increased affinity for an acidic pH microenvironment can take advantage of pathological conditions of inflammation for selective targeting. Recently, Rinaldi et al [21,22] have described the formulation of pH-sensitive niosomes containing Polysorbate 20/Chems (Tween 20, Tw20) or Polysorbate 20 derivatized by Glycine (Tw20-Gly) as an effective strategy for the delivery of anaesthetics and anti-inflammatory drugs. In particular, the preparation steps (panel A) and mechanism of bilayer destabilization (panel B) are shown in Figure 1.…”

Study to Investigate the anti-inflammatory effect of Codelac® Broncho with Thymus Serpyllum (elixir) in comparison with reference drug Fenspiride (syrup) using accute Carrageenan-induced Paw Inflammation Model

“…In addition to ambroxol, which has a mucolytic and expectorant effect, the composition of Codelac ® Broncho with Thymus Serpyllum (elixir) includes sodium glycyrrhizinate and thyme extract, each of which has an anti-inflammatory effect (Bernela et al 2016, Marianecci et al 2014, Qadir et al 2016. Their combined application is assumed to lead to synergy, as a result of which Codelac ® Broncho with Thymus Serpyllum (elixir) is able to have a pronounced anti-inflammatory effect.…”