Nanoemulgel, an Innovative Carrier for Diflunisal Topical Delivery with Profound Anti-Inflammatory Effect: in vitro and in vivo Evaluation

Int J Nanomedicine. 2021 Feb 22:16:1457-1472. doi: 10.2147/IJN.S294653. eCollection 2021.

Abstract

Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity.

Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model.

Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity.

Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.

Keywords: anti-inflammatory activity; diflunisal; improved efficacy; in vitro skin permeation; nanoemulsion; pseudoternary phase diagram.

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Carrageenan
  • Diflunisal / administration & dosage*
  • Diflunisal / chemistry
  • Diflunisal / pharmacology
  • Diflunisal / therapeutic use
  • Disease Models, Animal
  • Drug Compounding
  • Drug Delivery Systems*
  • Drug Liberation
  • Edema / drug therapy
  • Edema / pathology
  • Electric Conductivity
  • Emulsions / chemistry*
  • Hydrogen-Ion Concentration
  • Male
  • Nanogels / chemistry*
  • Particle Size
  • Permeability
  • Phase Transition
  • Polyethylene Glycols / chemistry*
  • Polyethyleneimine / chemistry*
  • Rats
  • Skin / drug effects
  • Skin Absorption / drug effects
  • Solubility
  • Surface-Active Agents / chemistry
  • Viscosity

Substances

  • Anti-Inflammatory Agents
  • Emulsions
  • Nanogels
  • Surface-Active Agents
  • polyethylene glycol polyethyleneimine nanogel
  • Polyethylene Glycols
  • Diflunisal
  • Carrageenan
  • Polyethyleneimine

Grants and funding

This study was sponsored by Higher Education Commission (HEC), Pakistan grant no. 417-71915-2MD4-010 (50039076).