title: Highly site-selective transvascular drug delivery by the use of nanosecond pulsed laser-induced photomechanical waves.
abstract: Photomechanical waves (PMWs), which were generated by irradiation of a light-absorbing material (laser target) with nanosecond laser pulses, were used for targeted transvascular drug delivery in rats. An Evans blue (EB) solution was injected into the tail vein, and laser targets were placed on the skin, muscle and brain. Each laser target was irradiated with a laser pulse(s) and 4h later, the rat was perfused and the distribution of EB fluorescence in the targeted tissues was examined. We observed laser fluence-dependent and hence PMW pressure-dependent extravasation of EB selectively in the tissues that had been exposed to a PMW(s). Uptake of leaked EB into cells in extravascular space was also observed in the targeted tissues. Tissue damage or hemorrhage was not apparent except in the brain exposed to the highest laser fluence used. The results for the brain indicated opening of the blood-brain barrier (BBB). Reverse-order (PMW application before EB injection) experiments showed that the BBB was closed in the duration from 8h to 12h after PMW application at a laser fluence of 0.5J/cm(2). Since EB molecules are strongly bound with serum albumin in blood, the results indicate that the present method can be applied not only to small molecules but also to macromolecules.
authors.affiliation: Division of Biomedical Information Sciences, National Defense Medical College Research Institute, 3-2, Namiki, Tokorozawa-shi, Saitama 359-8513, Japan. Electronic address: shunsato@ndmc.ac.jp.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sato
authors.affiliation: School of Integrated Design Engineering, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Biomedical Information Sciences, National Defense Medical College Research Institute, 3-2, Namiki, Tokorozawa-shi, Saitama 359-8513, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kawauchi
authors.affiliation: Japan Self Defense Forces Central Hospital, 1-2-24, Ikejiri, Setagaya-ku, Tokyo 154-8532, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Hosoe
authors.affiliation: School of Integrated Design Engineering, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Akutsu
authors.affiliation: Department of Dermatology, National Defense Medical College, 3-2, Namiki, Tokorozawa-shi, Saitama 359-8513, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Fujimoto
authors.affiliation: Division of Neurosurgery, Tokorozawa Central Hospital, 753-2, Kitaakitsu, Tokorozawa-shi, Saitama 359-0038, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nawashiro
authors.affiliation: School of Integrated Design Engineering, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Terakawa
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005070:Evans Blue / Q000008:administration & dosage*; D007834:Lasers; D008297:Male; D009132:Muscles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism
chemical_list: D005070:Evans Blue
keywords: Blood–brain barrier; Evans blue (PubChem CID: 6321418); Muscle; Nanosecond pulsed laser; Photomechanical wave; Skin; Transvascular drug delivery