Nano-Sized Ultrasound Contrast Agent: Salting-Out Method

Tumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs), stabilized, gas-filled bodies. They are generally less than 7 μm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of an...

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Main Authors: Margaret A. Wheatley, John Lewandowski
Format: Article
Language:English
Published: SAGE Publishing 2010-03-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2010.00007
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author Margaret A. Wheatley
John Lewandowski
author_facet Margaret A. Wheatley
John Lewandowski
author_sort Margaret A. Wheatley
collection DOAJ
description Tumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs), stabilized, gas-filled bodies. They are generally less than 7 μm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of angiogenic vessels. We describe the development of an echogenic, nano-sized polylactic acid UCA by adaptation of a salting-out method. The viscosity of the initial colloidal suspension (concentration and molecular weight of protective colloid [polyvinyl alcohol (PVA)] and concentration of polymer) was key in determining particle size and polydispersity (increasing viscosity increased both). Addition of the porogens ammonium carbonate and camphor, required to produce hollow echogenic capsules, also increased the size (eg, 5 wt% PVA, mean solid nanocapsule size 386 ± 25 nm, polydispersity index 0.367 ± 0.14, and mean UCA size 640 ± 18 nm, polydispersity index 0.308 ± 0.027). Viscosity had the opposite effect on echogenicity of the resultant nano-UCA, which ranged from 21.69 ± 0.78 dB for 2% PVA to 12.1 ± 0.8 dB for 10% PVA. The UCA prepared with 10% PVA, however, had a longer half-life in the ultrasound beam (t ½ > 15 minutes vs t ½ < 10 minutes), suggesting a thicker shell. Optimization will require compromise among size, echogenicity, and stability.
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spelling doaj-art-b7b9c2aa6bca45a6bcb5d56f737c47942025-01-02T22:37:25ZengSAGE PublishingMolecular Imaging1536-01212010-03-01910.2310/7290.2010.0000710.2310_7290.2010.00007Nano-Sized Ultrasound Contrast Agent: Salting-Out MethodMargaret A. WheatleyJohn LewandowskiTumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs), stabilized, gas-filled bodies. They are generally less than 7 μm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of angiogenic vessels. We describe the development of an echogenic, nano-sized polylactic acid UCA by adaptation of a salting-out method. The viscosity of the initial colloidal suspension (concentration and molecular weight of protective colloid [polyvinyl alcohol (PVA)] and concentration of polymer) was key in determining particle size and polydispersity (increasing viscosity increased both). Addition of the porogens ammonium carbonate and camphor, required to produce hollow echogenic capsules, also increased the size (eg, 5 wt% PVA, mean solid nanocapsule size 386 ± 25 nm, polydispersity index 0.367 ± 0.14, and mean UCA size 640 ± 18 nm, polydispersity index 0.308 ± 0.027). Viscosity had the opposite effect on echogenicity of the resultant nano-UCA, which ranged from 21.69 ± 0.78 dB for 2% PVA to 12.1 ± 0.8 dB for 10% PVA. The UCA prepared with 10% PVA, however, had a longer half-life in the ultrasound beam (t ½ > 15 minutes vs t ½ < 10 minutes), suggesting a thicker shell. Optimization will require compromise among size, echogenicity, and stability.https://doi.org/10.2310/7290.2010.00007
spellingShingle Margaret A. Wheatley
John Lewandowski
Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
Molecular Imaging
title Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
title_full Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
title_fullStr Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
title_full_unstemmed Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
title_short Nano-Sized Ultrasound Contrast Agent: Salting-Out Method
title_sort nano sized ultrasound contrast agent salting out method
url https://doi.org/10.2310/7290.2010.00007
work_keys_str_mv AT margaretawheatley nanosizedultrasoundcontrastagentsaltingoutmethod
AT johnlewandowski nanosizedultrasoundcontrastagentsaltingoutmethod