Fractional Thermolysis by Bipolar Radiofrequency Facilitates Cutaneous Delivery of Peptide and siRNA with Minor Loss of Barrier Function

Woan Ruoh Lee, Shing Chuan Shen, Chi Kuang Sun, Ibrahim A. Aljuffali, Shih Yun Suen, Yin Ku Lin, Jhi Joung Wang, Jia You Fang

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Purpose: In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. Methods: The morphology of the skin was examined by transmission electron microscopy (TEM), higher harmonic generation microscopy (HGM), and physiological factors. In vivo skin distribution of macromolecules was assessed by fluorescence and confocal microscopies. Results: RF thermolysis selectively created an array of micropores deep into the epidermis without significant removal of the stratum corneum (SC). With energy of 30 mJ, a pore depth of 35 μm was achieved. The bipolar RF resulted in a 3-fold increase of transepidermal water loss (TEWL) compared with intact skin. The respective skin accumulation and flux of the peptide with a molecular weight (MW) of 2335 Da was 3- and 23-fold greater for the RF-treated group than for the non-treatment group. RF enhanced skin accumulation of siRNAs with MW of 10 and 15 kDa by 6.2- and 2.6-fold, respectively. Cutaneous penetration of the macromolecules with an MW of at least 40 kDa could be accomplished by RF. Confocal microscopy imaging revealed that RF could effectively deliver the peptide up to at least a 74-μm depth. The penetration depth of siRNA by RF irradiation was about 50 μm. Conclusions: The novel RF device efficiently delivered macromolecules into the skin while reserving SC layers to support some barrier functions. In this work, for the first time the assistance of fractional RF on peptide and siRNA transport was demonstrated.

Original languageEnglish
Pages (from-to)1704-1713
Number of pages10
JournalPharmaceutical Research
Issue number5
Publication statusPublished - May 1 2015


  • fractional ablation
  • peptide
  • radiofrequency
  • siRNA
  • skin permeation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Molecular Medicine
  • Biotechnology
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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