Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA Microneedles and Fractional Ablative Laser

Pharm Res. 2018 Feb 21;35(3):68. doi: 10.1007/s11095-018-2369-6.


Purpose: This study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser.

Methods: PLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin.

Results: Both physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05).

Conclusions: Both fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin. Graphical Abstract ᅟ.

Keywords: characterization; fractional ablative laser; methotrexate; polymeric biodegradable microneedles; skin delivery.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / pharmacokinetics
  • Drug Delivery Systems / instrumentation*
  • Drug Delivery Systems / methods
  • Humans
  • Lasers
  • Lasers, Solid-State
  • Methotrexate / administration & dosage*
  • Methotrexate / pharmacokinetics
  • Microscopy, Electron, Scanning
  • Needles
  • Permeability
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / ultrastructure
  • Swine
  • Water Loss, Insensible / drug effects


  • Dermatologic Agents
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Methotrexate