title: Multi-beam laser-induced hydrodynamic shock waves used for delivery of microparticles and liquids in skin.
abstract: OBJECTIVE
  Laser radiation is often used to provide micro and nanoparticle delivery into the skin for medical and cosmetic purposes. This technique inherently has limited speed and effective penetration. We proposed and investigated a new method of rapid delivery of solid microparticles, nanoparticles and liquids into tissue through multiple microchannels created by a fractional laser microablation (FLMA) using Er:YAG-laser. The dependence of microchannel depth on laser pulse temporal structure and number of pulses and dermal coloration changes are studied in this paper.
  
  
  METHODS
  Microchannels created in the porcine skin in vitro by a fractional Er:YAG-laser were used to deliver Zirconium oxide (ZrO2) microparticles or hydrocortisone solution. Each laser pulse consisted of subpulses. Number of laser pulses (Np) and subpulses (Nsp) can be adjusted. The enhancement of delivery is expected due to hydrodynamic impact of laser pulse on the layer of the aqueous suspension of the particles or hydrocortisone solution placed on the skin surface. For color investigation, we used standard CIE Lab parameter analysis.
  
  
  RESULTS
  The relationship between microchannel depth in the skin and number of laser pulses and subpulses was established. We found that free filling of microchannels with ZrO2-particle suspension has a low speed of ∼4 × 10(-5)  mm/s. Particle delivery into microchannels induced by the hydrodynamic shock waves generated by Er:YAG-laser pulses is carried out with a high speed of 28.5 mm/s. We also found that skin color at ZrO2 -particle delivery differs from color of the intact skin, namely: the parameter L, which characterizes the "lightness" increased by 9 ± 1%; parameter a, which characterizes the "redness" decreased by 38 ± 4%; and parameter b, which characterizes the "yellowness" decreased by 21 ± 2%. The effective delivery of hydrocortisone was demonstrated using fluorescence method technique.
  
  
  CONCLUSIONS
  Multi-beam laser-induced hydrodynamic shock waves generated by Er:YAG-laser pulses on the layer of the aqueous suspension of the particles or solution of a high molecular weight drug placed on the skin can be used for their rapid delivery into the skin.
authors.affiliation: Saint Petersburg National Research University of Information Technologies, Mechanics and Optics, Saint-Petersburg, 197101, Russian Federation.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Belikov
authors.affiliation: Saint Petersburg National Research University of Information Technologies, Mechanics and Optics, Saint-Petersburg, 197101, Russian Federation.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Skrypnik
authors.affiliation: Saint Petersburg National Research University of Information Technologies, Mechanics and Optics, Saint-Petersburg, 197101, Russian Federation.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Shatilova
authors.affiliation: Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, 410012, Russian Federation.|Institute of Precise Mechanics and Control of Russian Academy of Sciences, Saratov, 410028, Russian Federation.|Laboratory of Biophotonics, Tomsk State University, Tomsk, 634050, Russian Federation.
authors.forename: Valery V
authors.initials: VV
authors.lastname: Tuchin
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D019220:High-Energy Shock Waves; D006854:Hydrocortisone / Q000008:administration & dosage*; D057446:Hydrodynamics; D053844:Lasers, Solid-State; D053758:Nanoparticles / Q000008:administration & dosage*; D013552:Swine; D046509:Tissue Culture Techniques
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D006854:Hydrocortisone
keywords: Er:YAG-laser; fractional laser microablation (FLMA); hydrocortisone; microchannels; microparticles; zirconium oxide