Design, preparation, and evaluation of liposomal gel formulations for treatment of acne: in vitro and in vivo studies

Drug Dev Ind Pharm. 2019 Mar;45(3):395-404. doi: 10.1080/03639045.2018.1546310. Epub 2018 Nov 30.

Abstract

The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of ∼100 nm and ∼14 mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60 days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that Tmax for curcumin was achieved within 1 h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted Cmax of 688.3 ng/mL and AUC0-t of 5857.5 h × ng/mL, while the skin samples displayed Cmax of 203.3 ng/gm and AUC0-t of 2938.1 h × ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed ∼1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a ∼2 fold reduction in comedones count and cytokines (TNF-α and IL-1β) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.

Keywords: Carbopol; Curcumin; lauric acid; liposomes.

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Azithromycin / pharmacokinetics
  • Azithromycin / pharmacology
  • Chemistry, Pharmaceutical / methods
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics
  • Curcumin / pharmacology
  • Gels / chemistry*
  • Gels / pharmacokinetics
  • Gels / pharmacology*
  • Lauric Acids / chemistry
  • Lauric Acids / pharmacokinetics
  • Lauric Acids / pharmacology
  • Liposomes / chemistry*
  • Liposomes / pharmacokinetics
  • Liposomes / pharmacology*
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects

Substances

  • Anti-Bacterial Agents
  • Gels
  • Lauric Acids
  • Liposomes
  • lauric acid
  • Azithromycin
  • Curcumin