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• W2154328382 abstract "<para xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink> Low delivery efficiency combined with systemic toxicity of traditional chemotherapy provides a need for improved chemotherapeutic delivery. Within our laboratory, we have developed polymer ultrasound contrast agents (1.2–1.8 <formula formulatype=inline><tex Notation=TeX>$mu$</tex></formula>m in diameter) containing doxorubicin (Dox) within the shell (100–150 nm). <emphasis emphasistype=italic>In vivo</emphasis> this platform is expected to circulate through the vasculature until activated at the tumor site with external focused ultrasound (US). <emphasis emphasistype=italic>In vitro</emphasis>, the agent is responsive to US and when insonated at peak positive pressure amplitudes of 0.69 MPa and above, shows dramatic size reduction, eventually reaching a mean particle size of 350 nm, presumably due to fragmentation of, or gas release from the agent. The resulting Dox-polymer particles retain the drug and are small enough to pass through the leaky pores (350–400 nm) within the tumor vasculature, providing a sustained intratumoral release of chemotherapeutic as the polymer degrades. <emphasis emphasistype=italic>In vivo</emphasis> studies using a VX2 liver tumor model have shown that the combination of the agent and US results in nearly 50% less drug delivered to the nontargeted, healthy liver ( <formula formulatype=inline><tex Notation=TeX>$p$</tex></formula> <formula formulatype=inline><tex Notation=TeX>$=$</tex></formula> 0.009) and a 110% increase (<formula formulatype=inline><tex Notation=TeX>$p$</tex></formula> <formula formulatype=inline><tex Notation=TeX>$=$ </tex></formula> 0.004) in Dox delivery to the viable peripheral tissue of the tumor, relative to the uninsonated controls. This study shows how US-mediated destruction of drug-loaded polymer contrast agent can be used to deliver encapsulated drug for potential sustained release. Penetration mechanisms of these resulting particles and their ability to provide a sustained release from the tumor interstia will be explored in the future. </para>" @default.
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• W2154328382 date "2010-01-01" @default.
• W2154328382 modified "2023-10-18" @default.
• W2154328382 title "Delivery of Encapsulated Doxorubicin by Ultrasound-Mediated Size Reduction of Drug-Loaded Polymer Contrast Agents" @default.
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• W2154328382 doi "https://doi.org/10.1109/tbme.2009.2030497" @default.
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