title: Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study.
abstract: Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.
authors.affiliation: Department of Biomedical Engineering, Yonsei University, Wonju, Korea.
authors.forename: Donghee
authors.initials: D
authors.lastname: Park
authors.forename: Heungil
authors.initials: H
authors.lastname: Ryu
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Park
authors.forename: Jongbum
authors.initials: J
authors.lastname: Seo
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005466:Fluorocarbons / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010539:Permeability; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000502:physiology; D013010:Sonication; D013459:Sulfur Hexafluoride / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride; C042852:perflutren