Echogenic liposomes (ELIPs) are an excellent candidate for ultrasound activated therapeutics and imaging. Although multiple experiments have established their echogenicity, the underlying mechanism has remained unknown. However, freeze-drying in the presence of mannitol during ELIP preparation has proved critical to ensuring echogenicity. Here, the role of this key component in the preparation protocol was investigated by measuring scattering from freshly prepared freeze-dried aqueous solution of mannitol—and a number of other excipients commonly used in lyophilization—directly dispersed in water without any lipids in the experiment. Mannitol, meso-erythritol, glycine, and glucose that form a highly porous crystalline phase upon freeze-drying generated bubbles resulting in strong echoes during their dissolution. On the other hand, sucrose, trehalose, and xylitol, which become glassy while freeze-dried, did not. Freeze-dried mannitol and other crystalline substances, if thawed before being introduced into the scattering volume, did not produce echogenicity, as they lost their crystallinity in the thawed state. The echogenicity disappeared in a degassed environment. Higher amounts of sugar in the original aqueous solution before freeze-drying resulted in higher echogenicity because of the stronger supersaturation and crystallinity. The bubbles created by the freeze-dried mannitol in the ELIP formulation play a critical role in making ELIPs echogenic.
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December 2017
December 19 2017
Role of freeze-drying in the presence of mannitol on the echogenicity of echogenic liposomes
Krishna N. Kumar;
Krishna N. Kumar
1
Department of Mechanical and Aerospace Engineering, The George Washington University
, Washington DC 20052, USA
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Sanku Mallik;
Sanku Mallik
2
Department of Pharmaceutical Sciences, North Dakota State University
, Fargo, North Dakota 58102, USA
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Kausik Sarkar
1
Department of Mechanical and Aerospace Engineering, The George Washington University
, Washington DC 20052, USA
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a)
Electronic mail: sarkar@gwu.edu
J. Acoust. Soc. Am. 142, 3670–3676 (2017)
Article history
Received:
June 08 2017
Accepted:
November 23 2017
Citation
Krishna N. Kumar, Sanku Mallik, Kausik Sarkar; Role of freeze-drying in the presence of mannitol on the echogenicity of echogenic liposomes. J. Acoust. Soc. Am. 1 December 2017; 142 (6): 3670–3676. https://doi.org/10.1121/1.5017607
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