Ultrasonography.  2015 Oct;34(4):297-303. 10.14366/usg.15009.

Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery

• Yoon YI
• Yoon TJ
• Lee HJ

• KMID: 2381997
• DOI: http://doi.org/10.14366/usg.15009

Abstract

PURPOSE
The aim of this study was to identify the optimal ultrasound (US) parameters for gene and drug delivery.
METHODS
In order to target SkBr3, which is a breast cancer cell overexpressing the Her2 receptor, trastuzumab (Herceptin) was used. Micobubble-nanoliposome complex (MLC) was mixed with trastuzumab and stored overnight. Finally, MLC was combined with Her2Ab. A US device equipped with a 1-MHz probe was used for delivery to the cell. Several parameters, including intensity (w/cm2), time (minutes), and duty cycle (%), were varied within a range from 1 w/cm2, 1 minute, and 20% to 2 w/cm2, 2 minutes, and 60%, respectively. A confocal laser scanning microscope (CLSM) was used to confirm the delivery of MLC to the cells after US treatment.
RESULTS
MLC with fluorescent dyes and trastuzumab was synthesized successfully. By delivering MLC with Her2Ab to cells, the targeting effect of trastuzumab with MLC was confirmed by CLSM. The cell membranes showed green (fluorescein isothiocyanate) and red (Texas red) fluorescence but treatments with MLC without Her2Ab did not show any fluorescence. Optimal conditions for US-mediated delivery were 1 or 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.9% for 1 w/cm2 and 95.7% for 2 w/cm2) for hydrophobic materials and 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.0%) for hydrophilic materials.
CONCLUSION
The greater the strength, duty cycle, and period of US application within the tested range, the more efficiently the fluorescent contents were conveyed.

Keyword

Microbubbles; Liposomes; Therapy, image-guided; Ultrasound

MeSH Terms

Breast Neoplasms
Cell Membrane
Fluorescence
Fluorescent Dyes
Liposomes
Microbubbles
Ultrasonography*
Trastuzumab
Fluorescent Dyes
Liposomes