Effects of Microbubble Size on Ultrasound-Induced Transdermal Delivery of High-Molecular-Weight Drugs

Abstract

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 μm) 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/cm2 the penetration depth in group US combined with 3.5-μm MBs and penetrating VC-IP (U+3.5) was 34% and 14% higher than those in groups US combined with 1.4-μm MBs and penetrating VC-IP (U+1.4) and US combined with 2.1-μm 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.

Strategies in Development and Delivery of Nanotechnology Based Cosmetic Products

“…Molecular size and shape The molecular weight of a chemical is a good indicator of its molecular size, which, in turn, is related to the diffusion coefficient according to the Stokes-Einstein relation. As drug diffusion through the skin is a passive mechanism, small molecules traverse the human skin faster than larger molecules [15]. Therefore, candidates for transdermal delivery should have a molecular weight not higher than 500 Dalton.…”

Recent advances in ultrasound-based transdermal drug delivery

“…2 Transdermal drug delivery offers several advantages to address issues associated with oral delivery and hypodermic injections through the application of specialized medicated adhesive patches onto the skin. 3 However, there are several limitations associated with transdermal drug delivery systems. The efficacy and implementation of transdermal drug delivery is principally limited by the physical barrier of the skin.…”

Low-frequency dual-frequency ultrasound-mediated microbubble cavitation for transdermal minoxidil delivery and hair growth enhancement

“…A previous study demonstrated that US-assisted vaccine delivery in the presence of sub-micron cavitation nuclei resulted higher specific antibody levels compared to other transdermal methods 14 . Our previous studies demonstrated that combined treatment with US using optimal parameters and optimal conditions (size or concentration) of microbubbles (MBs) can increase skin permeability so as to enhance drug delivery without increasing temperatures or causing heating damage 15,16 . Minoxidil (Mx)-coated albumin-shelled MBs produced in a layer-by-layer manner combined with sonication by US energy in the water phase successively enhanced hair growth while shortening the treatment period 17 .…”