title: Therapeutic effects of paclitaxel-containing ultrasound contrast agents.
abstract: Drug delivery vehicles that combine ultrasonic and molecular targeting are shown to locally concentrate a drug in a region-of-interest. The drug delivery vehicles, referred to as acoustically active lipospheres (AALs), are microbubbles surrounded by a shell of oil and lipid. In a region limited to the focal area of ultrasound application, circulating AALs are deflected by radiation force to a vessel wall and can subsequently be fragmented. Ligands targeting the alphavbeta3 integrin are conjugated to the AAL shell and increase in vitro binding by 26.5-fold over nontargeted agents. Toxicity assays demonstrate that paclitaxel-containing AALs exert a greater antiproliferative effect after insonation than free paclitaxel at an equivalent concentration. Lastly, ultrasound and molecular targeting are combined to deliver a model drug to the endothelium and interstitium of chorioallantoic membrane vasculature in vivo.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Michaelann Shortencarier
authors.initials: MS
authors.lastname: Tartis
authors.forename: Jennifer
authors.initials: J
authors.lastname: McCallan
authors.forename: Aaron F H
authors.initials: AF
authors.lastname: Lum
authors.forename: Rachel
authors.initials: R
authors.lastname: LaBell
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Stieger
authors.forename: Terry O
authors.initials: TO
authors.lastname: Matsunaga
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016923:Cell Death / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D003287:Contrast Media; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008024:Ligands; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D045423:Microbubbles; D009363:Neoplasm Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013010:Sonication; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D008024:Ligands; D009363:Neoplasm Proteins; D017239:Paclitaxel