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 journalArticle

9 Citations (Scopus)

Abstract

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
Volume32
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Thermolysis
Small Interfering RNA
Skin
Peptides
Macromolecules
Confocal microscopy
Molecular weight
Molecular Weight
Confocal Microscopy
Cornea
Fluorescence microscopy
Harmonic generation
Microchannels
Permeation
Transmission Electron Microscopy
Fluorescence Microscopy
Epidermis
Microscopic examination
Microscopy
Irradiation

Keywords

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

ASJC Scopus subject areas

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

Cite this

Fractional Thermolysis by Bipolar Radiofrequency Facilitates Cutaneous Delivery of Peptide and siRNA with Minor Loss of Barrier Function. / Lee, Woan Ruoh; Shen, Shing Chuan; Sun, Chi Kuang; Aljuffali, Ibrahim A.; Suen, Shih Yun; Lin, Yin Ku; Wang, Jhi Joung; Fang, Jia You.

In: Pharmaceutical Research, Vol. 32, No. 5, 01.05.2015, p. 1704-1713.

Research output: Contribution to journalArticle

Lee, Woan Ruoh ; Shen, Shing Chuan ; Sun, Chi Kuang ; Aljuffali, Ibrahim A. ; Suen, Shih Yun ; Lin, Yin Ku ; Wang, Jhi Joung ; Fang, Jia You. / Fractional Thermolysis by Bipolar Radiofrequency Facilitates Cutaneous Delivery of Peptide and siRNA with Minor Loss of Barrier Function. In: Pharmaceutical Research. 2015 ; Vol. 32, No. 5. pp. 1704-1713.
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AU - Lee, Woan Ruoh

AU - Shen, Shing Chuan

AU - Sun, Chi Kuang

AU - Aljuffali, Ibrahim A.

AU - Suen, Shih Yun

AU - Lin, Yin Ku

AU - Wang, Jhi Joung

AU - Fang, Jia You

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N2 - 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.

AB - 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.

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