中国物理B ›› 2016, Vol. 25 ›› Issue (12): 124314-124314.doi: 10.1088/1674-1056/25/12/124314

• SPECIAL TOPIC—Acoustics • 上一篇    下一篇

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Huan-Lei Wang(王焕磊), Peng-Fei Fan(范鹏飞), Xia-Sheng Guo(郭霞生), Juan Tu(屠娟), Yong Ma(马勇), Dong Zhang(章东)   

  1. 1. Key Laboratory of Modern Acoustics(Nanjing University), Ministry of Education, Nanjing 210093, China;
    2. Department of Applied Engineering, Zhejiang Business College, Hangzhou 310053, China;
    3. Institute of Traumatology and Orthopedics, Nanjing University of Chinese Medicine, Nanjing 210023, China
  • 收稿日期:2016-05-31 修回日期:2016-08-29 出版日期:2016-12-05 发布日期:2016-12-05
  • 通讯作者: Juan Tu, Yong Ma E-mail:juantu@nju.edu.cn;yongma@126.com
  • 基金资助:

    Project partially supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 81473692, 81673995, 11374155, 11574156, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK2011812), the Fundamental Research Funds for the Central Universities, and the National High-Tech Research and Development Program of China (Grant No. 2012AA022702).

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Huan-Lei Wang(王焕磊)1,2, Peng-Fei Fan(范鹏飞)1, Xia-Sheng Guo(郭霞生)1, Juan Tu(屠娟)1, Yong Ma(马勇)1, Dong Zhang(章东)3   

  1. 1. Key Laboratory of Modern Acoustics(Nanjing University), Ministry of Education, Nanjing 210093, China;
    2. Department of Applied Engineering, Zhejiang Business College, Hangzhou 310053, China;
    3. Institute of Traumatology and Orthopedics, Nanjing University of Chinese Medicine, Nanjing 210023, China
  • Received:2016-05-31 Revised:2016-08-29 Online:2016-12-05 Published:2016-12-05
  • Contact: Juan Tu, Yong Ma E-mail:juantu@nju.edu.cn;yongma@126.com
  • Supported by:

    Project partially supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 81473692, 81673995, 11374155, 11574156, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK2011812), the Fundamental Research Funds for the Central Universities, and the National High-Tech Research and Development Program of China (Grant No. 2012AA022702).

摘要:

Transdermal drug delivery (TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful.

关键词: transdermal delivery of drugs, ultrasound contrast agents, pulsed ultrasound, cavitation effect

Abstract:

Transdermal drug delivery (TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful.

Key words: transdermal delivery of drugs, ultrasound contrast agents, pulsed ultrasound, cavitation effect

中图分类号:  (Bioacoustics)

  • 43.80.+p
87.50.Y- (Biological effects of acoustic and ultrasonic energy) 43.25.+y (Nonlinear acoustics)