Dithranol-loaded nanostructured lipid carrier-based gel ameliorate psoriasis in imiquimod-induced mice psoriatic plaque model

Drug Dev Ind Pharm. 2019 May;45(5):826-838. doi: 10.1080/03639045.2019.1576722. Epub 2019 Feb 14.

Abstract

Objective: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation.

Significance: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis.

Methods: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol).

Results: NLCs were prepared with particle size below 300 nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ∼100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control.

Conclusions: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product.

Keywords: ELISA; IMQ induced psoriatic plaque model; Nanostructured lipid carriers; dithranol; gel; interleukins; staining property.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anthralin / administration & dosage*
  • Anthralin / pharmacokinetics
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / pharmacokinetics
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Gels
  • Humans
  • Imiquimod / administration & dosage
  • Imiquimod / immunology
  • Lipids / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Ointments
  • Particle Size
  • Psoriasis / diagnosis
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Severity of Illness Index
  • Skin / drug effects
  • Skin / pathology
  • Treatment Outcome

Substances

  • Dermatologic Agents
  • Drug Carriers
  • Gels
  • Lipids
  • Ointments
  • Imiquimod
  • Anthralin