Qualitative and quantitative analysis of lateral diffusion of drugs in human skin

Int J Pharm. 2018 Jun 10;544(1):62-74. doi: 10.1016/j.ijpharm.2018.04.013. Epub 2018 Apr 11.


This study aimed to qualitatively and quantitatively analyze lateral diffusion of drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue dyes in skin was investigated using confocal laser microscopy, calcein imaging, and histology studies. In in vitro permeation studies, two linear microdialysis probes were inserted into the dermis of untreated, poly lacto-glycolic acid microneedle-treated, and ablative laser-treated skin such that one was in the center of the diffusion area and the other was parallel, at 8 mm from the central probe. Skin was mounted on Franz cells, sandwiched between donor containing diclofenac sodium solution and receptor containing phosphate buffered saline, pH 7.4. Qualitative techniques revealed faster lateral diffusion of the dyes in microneedle-treated skin than laser-treated skin. Rate of drug diffusion in the central probe in the microneedle-treated skin (11.8 ± 2.5 μg/h) was significantly higher than untreated and laser-treated skin (p < 0.05). Rate of lateral diffusion in untreated group (0.7 ± 0.1 μg/h) was significantly lower than microneedle and laser-treated skin (p < 0.05). Overall, in vitro microdialysis was demonstrated as a novel and valuable tool that can be employed for quantitative investigation of rate of vertical and lateral diffusion of drugs in intact and microporated skin.

Keywords: Ablative laser; Diclofenac Sodium (PubChem CID: 5018304); In vitro permeation; Lateral diffusion; Microdialysis; Microneedles; Transdermal.

MeSH terms

  • Administration, Cutaneous
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Coloring Agents / administration & dosage
  • Coloring Agents / pharmacokinetics
  • Diclofenac / administration & dosage
  • Diclofenac / pharmacokinetics
  • Diffusion
  • Fluoresceins / administration & dosage
  • Fluoresceins / pharmacokinetics
  • Humans
  • In Vitro Techniques
  • Lasers
  • Methylene Blue / administration & dosage
  • Methylene Blue / pharmacokinetics
  • Microinjections
  • Needles
  • Permeability
  • Skin / metabolism*
  • Skin Absorption*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Coloring Agents
  • Fluoresceins
  • Diclofenac
  • Methylene Blue
  • fluorexon