Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 32, Issue 11, Pages 1771-1780Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2006.03.017
Keywords
targeted drug delivery; paclitaxel; ultrasound contrast agents; radiation force; alpha(v)beta(3); acoustically active lipospheres (AALs); angiogenesis
Funding
- NCI NIH HHS [R01 CA112356, CA 103828, R01 CA103828] Funding Source: Medline
- NIBIB NIH HHS [EB 2952] Funding Source: Medline
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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 alpha(v)beta(3) 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.
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