In previous studies, we have found that addition of cavitation seed such as ultrasound contrast agents (UCA) in sonophoresis accelerate and increase efficiency of transdermal drug delivery (TDD). Actively-induced cavitation with low intensity ultrasound (less than 1 MPa) on the skin causes disordering of the lipid bilayers and the formation of aqueous channels. However, commercial UCAs also have limit, because mixed UCA is uniformly positioned in the water based solution, not on the skin surface. In order to enhance the TDD, the cavitation effect of cavitation seed should be generated near skin surface. For that reason, we manufactured specialized cavitation seed for TDD, which can be sank near skin surface by gravity. In order to make sure possibility of macromolecules delivery using cavitation seed, we performed in vivo experiment using sonophoresis with specialized cavitation seed.