Development and in vitro assessment of psoralen and resveratrol co-loaded ultradeformable liposomes for the treatment of vitiligo

J Photochem Photobiol B. 2017 Sep:174:44-57. doi: 10.1016/j.jphotobiol.2017.07.007. Epub 2017 Jul 12.

Abstract

Vitiligo is a de-pigmenting skin disorder characterized by white patches on skin due to partial or complete loss of melanocytes. Psoralen in combination with ultraviolet-A (PUVA) acts by stimulation of melanin content and tyrosinase activity in melanocytes. Resveratrol, a sirtuin activator and a potential anti-oxidant reduce oxidative stress which is one of the triggering factors for initiation of vitiligo. Despite their therapeutic activity, weak percutaneous permeability of psoralen and poor solubility of resveratrol hinders their effective topical administration. The aim of present study is to formulate ultradeformable liposomes (UDL) co-loaded with psoralen and resveratrol for evaluation of PUVA and anti-oxidant combination in vitiligo treatment. For this purpose, UDL composed of DC-Chol, cholesterol and sodium deoxy cholate were prepared for their co-delivery. Liposomal carriers were characterized and evaluated for their efficacy using B16F10 cell line. Free radical scavenging potential was also determined for these carriers by in vitro anti-oxidant assays. Optimal co-loaded UDL with particle size ranging from 120 to 130nm, zeta potential of +46.2mV, entrapment efficiency of 74.09% (psoralen) and 76.91% (resveratrol) were obtained. Compared to control, co-loaded UDL showed significant stimulation of melanin and tyrosinase activity with major contribution of psoralen. Further, co-loaded UDL also exhibited potential free radical scavenging activity where resveratrol played a key role. Hence, psoralen and resveratrol co-loaded UDL acts in vitiligo through dual mechanisms of action viz., stimulation of melanin and tyrosinase activity as well as by anti-oxidant activity. These findings indicate that psoralen and resveratrol co-loaded UDL has the promising therapeutic potential for the treatment of vitiligo.

Keywords: Anti-oxidant; Melanin; PUVA; Resveratrol; Tyrosinase; Ultradeformable liposomes; Vitiligo.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Compounding
  • Drug Liberation
  • Ficusin / chemistry*
  • Ficusin / metabolism
  • Ficusin / pharmacology*
  • Ficusin / therapeutic use
  • Kinetics
  • Liposomes
  • Melanins / metabolism
  • Mice
  • Monophenol Monooxygenase / metabolism
  • Particle Size
  • Resveratrol
  • Stilbenes / chemistry*
  • Stilbenes / metabolism
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • Vitiligo / drug therapy*
  • Vitiligo / metabolism

Substances

  • Liposomes
  • Melanins
  • Stilbenes
  • Monophenol Monooxygenase
  • Ficusin
  • Resveratrol