Luliconazole loaded lyotropic liquid crystalline nanoparticles for topical delivery: QbD driven optimization, in-vitro characterization and dermatokinetic assessment

Chem Phys Lipids. 2021 Jan:234:105028. doi: 10.1016/j.chemphyslip.2020.105028. Epub 2020 Dec 10.

Abstract

Fungal infections are an important cause of morbidity and pose a serious health concern especially in immunocompromised patients. Luliconazole (LUL) is a topical imidazole antifungal drug with a broad spectrum of activity. To overcome the limitations of conventional dosage forms, LUL loaded lyotropic liquid crystalline nanoparticles (LCNP) were formulated and characterized using a three-factor, five-level Central Composite Design of Response Surface Methodology. LUL loaded LCNP showed particle size of 181 ± 12.3 nm with an entrapment efficiency of 91.49 ± 1.61 %. The LUL-LCNP dispersion in-vitro drug release showed extended release up to 54 h. Ex-vivo skin permeation studies revealed transdermal flux value (J) of LUL-LCNP gel (7.582 μg/h/cm2) 2 folds higher compared to marketed cream (3.3706 μg/h/cm2). The retention of LUL in the stratum corneum was ∼1.5 folds higher and ∼2 folds higher in the epidermis and other deeper layers in comparison to the marketed cream. The total amount of drug penetrated (AUC0-∞) with LCNP formulation was 4.7 folds higher in epidermis and 6.5 folds higher in dermis than marketed cream. The study's findings vouch that LCNP can be a promising and effective carrier system for the delivery of antifungal drugs with enhanced skin permeation.

Keywords: Antifungal; Central composite design; Dermatokinetics; Fungal infections; Lipid nanoparticles; Liquid crystals; Luliconazole; Quality by design.

MeSH terms

  • Administration, Cutaneous
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry*
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / chemistry*
  • Liquid Crystals / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Skin / chemistry*
  • Skin / metabolism

Substances

  • Antifungal Agents
  • Imidazoles
  • luliconazole