Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis

J Liposome Res. 2020 Mar;30(1):68-79. doi: 10.1080/08982104.2019.1593449. Epub 2019 Apr 23.

Abstract

Cyclosporine (CYC), a calcineurin inhibitor acts specifically on T-cells and is one of the most effective treatment options for psoriasis. Systemic administration of the drug has been associated with dose-dependent toxic effects, while its topical delivery is a challenging task due to unfavourable physicochemical properties of drug. The aim of the present study is to develop and evaluate the efficacy of topical liposomal gel containing CYC loaded cationic liposomal nanocarriers in imiquimod induced psoriatic plaque model. Liposomes composed of DOTAP and cholesterol was formulated by different liposomal preparation techniques. Optimized liposomal carriers prepared by ethanol injection method were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Cationic liposomes with particle size of 111 ± 1.62 nm, PDI of 0.27 ± 0.08, entrapment efficiency of 93 ± 2.12%, and zeta potential of 41.12 ± 3.56 mV were obtained. Drug loaded liposomal gels showed shear thinning behaviour, which is suitable for topical application. Topical application of CYC liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumour necrosis factor-α, IL-17, and IL-22. In conclusion, the developed liposomal carrier of CYC was found to be effective and can find application in treatment of psoriasis.

Keywords: Cationic liposomes; cyclosporine; imiquimod induced psoriatic plaque model; psoriasis; topical delivery.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Cations / chemistry
  • Cholesterol / chemistry
  • Cyclosporine / administration & dosage
  • Cyclosporine / chemistry*
  • Cytokines / metabolism
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / chemistry*
  • Drug Compounding
  • Drug Liberation
  • Fatty Acids, Monounsaturated / chemistry
  • Humans
  • Hydrogels / chemistry
  • Liposomes / chemistry*
  • Male
  • Mice, Inbred BALB C
  • Nanocapsules / chemistry*
  • Psoriasis / drug therapy*
  • Quaternary Ammonium Compounds / chemistry
  • Skin / metabolism
  • Skin Absorption
  • Treatment Outcome

Substances

  • Cations
  • Cytokines
  • Dermatologic Agents
  • Fatty Acids, Monounsaturated
  • Hydrogels
  • Liposomes
  • Nanocapsules
  • Quaternary Ammonium Compounds
  • Cyclosporine
  • Cholesterol
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane