Laser-induced thermal coagulation enhances skin uptake of topically applied compounds

Lasers Surg Med. 2017 Aug;49(6):582-591. doi: 10.1002/lsm.22642. Epub 2017 Feb 9.

Abstract

Background: Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown.

Methods: Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro-needles (0 μm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 μm, CZ-20) and skin equilibrated to room temperature (80 μm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids.

Results: Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P < 0.001). In dermis, the uptake through CZ-20 channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 μm; P < 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ-20 compared to CZ-80 and CZ-0 samples (P < 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low.

Conclusion: Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: Franz cell; ablative fractional laser; coagulation zone; topical drug delivery.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Blood Coagulation*
  • Cells, Cultured
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / pharmacokinetics*
  • Drug Delivery Systems*
  • Female
  • Microscopy, Fluorescence
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics*
  • Random Allocation
  • Skin / diagnostic imaging
  • Skin / metabolism*
  • Swine

Substances

  • Dermatologic Agents
  • Polyethylene Glycols