Development of sulconazole-loaded nanoemulsions for enhancement of transdermal permeation and antifungal activity

Int J Nanomedicine. 2019 May 28:14:3955-3966. doi: 10.2147/IJN.S206657. eCollection 2019.

Abstract

Background: Sulconazole (SCZ) is a broad-spectrum transdermally administered anti-fungicidal agent. However, the therapeutic effect of SCZ is generally limited by its poor water solubility. This present study aimed to develop and evaluate sulconazole-loaded nanoemulsions (SCZ-NEs) for enhancement of the transdermal permeation and antifungal activity. Methods: A spontaneous titration method was applied to prepare the SCZ-NEs. And the optimized formulation of SCZ-NEs was screened by central composite design (CCD). In addition, the characteristics of the SCZ-NEs were evaluated, including particle size, zeta potential, drug loading (DL%) and encapsulation efficiency (EE%). The morphology of SCZ-NEs was observed by transmission electron microscopy (TEM). Franz diffusion cells were used to evaluate the transdermal permeability of the SCZ-NEs. The antifungal activity of the SCZ-NEs was measured by a zone of inhibition (ZOI) test. Results: The optimized SCZ-NEs possessed a moderate particle size of 52.3±3.8 nm, zeta potential of 23.3±1.2 mV, DL% of 0.47±0.05% and EE% of 87.1±3.2%. The ex vivo skin permeation study verified that the cumulative permeability (Qn) and penetration rate (Js) of the optimized SCZ-NEs were about 1.7-fold higher than that of a commercial reference, miconazole (MCZ) cream and 3-fold higher than that of SCZ-DMSO solution. The optimized SCZ-NEs exhibited zone of inhibition (ZOI) values of 23.5±2.4 and 20.4±2.5 mm against C. albicans and T. rubrum, which were larger compared with these of the MCZ cream and SCZ-DMSO solution. Conclusion: SCZ-NEs were effectively developed to overcome the poor solubility of SCZ, promote SCZ permeation through the skin and improve its antifungal activity. Thus, the SCZ-NEs are a promising percutaneous administration for skin fungal infections induced by C. albicans and T. rubrum.

Keywords: antifungal activity; central composite design; nanoemulsion; sulconazole; transdermal delivery.

MeSH terms

  • Administration, Cutaneous
  • Analysis of Variance
  • Animals
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects
  • Emulsions / chemistry*
  • Fungi / drug effects
  • Imidazoles / pharmacology*
  • Male
  • Microbial Sensitivity Tests
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Oils / chemistry
  • Particle Size
  • Permeability / drug effects
  • Phase Transition
  • Rats, Sprague-Dawley
  • Skin Absorption / drug effects*
  • Solubility
  • Surface-Active Agents / chemistry

Substances

  • Antifungal Agents
  • Emulsions
  • Imidazoles
  • Oils
  • Surface-Active Agents
  • sulconazole