期刊
PLOS ONE
卷 10, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0138500
关键词
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资金
- Ministry of Science and Technology, Taiwan [MOST103-2221-E-011-004-MY3, MOST101-2314-B-016-012-MY3]
- Tri-Service General Hospital [TSGH-NTUST-104-02, TSGH-C102-011]
- National Defense Medical Research grant [MAB102-40]
The transdermal delivery of a wide range of high-molecular-weight drugs is limited by the stratum corneum layer of the epidermis representing a significant barrier to penetration across the skin. This study first determined the different effects of different-size ultrasound (US) contrast agents and microbubbles (MBs) for enhancing the transdermal delivery of high-molecular-weight drugs. The effects of US-mediated different-size (1.4, 2.1, and 3.5 mu m) MBs (as a contrast agent) and ascorbyl tetraisopalmitate (VC-IP) on enhancing skin transdermal delivery were demonstrated both in vitro and in vivo. The results indicated that at a power density of 3 W/cm(2) the penetration depth in group US combined with 3.5-mu m MBs and penetrating VC-IP (U+3.5) was 34% and 14% higher than those in groups US combined with 1.4-mu m MBs and penetrating VC-IP (U+1.4) and US combined with 2.1-mu m MBs and penetrating VC-IP (U+2.1), respectively, for the agarose phantoms, while the corresponding increases for pigskin were 37% and 19%. In terms of the skin permeation of VC-IP, the VC-IP concentration in group U+3.5 was 23% and 10% higher in than those in groups U+1.4 and U+2.1, respectively. The whitening effect (luminosity index) of mice skin in group U+3.5 had increased (significantly) by 28% after 1 week, by 34% after 2 weeks, and tended to stabilize after 3 weeks (45%) in C57BL/6J mice over a 4-week experimental period. The results obtained in this study indicate that combining US with MBs of different sizes can produce different degrees of skin permeability so as to enhance the delivery of VC-IP to inhibit melanogenesis, without damaging the skin in mice.
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