Therapeutic effects of paclitaxel-containing ultrasound contrast agents.
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.
Tartis
Michaelann Shortencarier
MS
Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
McCallan
Jennifer
J
Lum
Aaron F H
AF
LaBell
Rachel
R
Stieger
Susanne M
SM
Matsunaga
Terry O
TO
Ferrara
Katherine W
KW
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
D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D008024:Ligands; D009363:Neoplasm Proteins; D017239:Paclitaxel