Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery.

The use of ultrasound has gained great interest for nucleic acids delivery. Ultrasound can reach deep tissues in non-invasive manner. The process of sonoporation is based on the use of low-frequency ultrasound combined with gas-filled microbubbles (MBs) allowing an improved delivery of molecules including nucleic acids in the insonified tissue. For in vivo gene transfer, the engineering of cationic MBs is essential for creating strong electrostatic interactions between MBs and nucleic acids leading to their protection against nucleases degradation and high concentration within the target tissue. Cationic MBs must be stable enough to withstand nucleic acids interaction, have a good size distribution for in vivo administration, and enough acoustic activity to be detected by echography. This review aims to summarize the basic principles of ultrasound-based delivery and new knowledge acquired in these recent years about this method. A focus is made on gene delivery by discussing reported studies made with cationic MBs including ours. They have the ability for efficient delivery of plasmid DNA (pDNA), mRNA or siRNA. Last, we discuss about the key challenges that have to be faced for a fine use of this delivery system.

Spatial variation of acoustic parameters in human skin: an in vitro study between 22 and 45 MHz.

This study of spatial variance of acoustic parameters was performed on eight nonfrozen samples of female abdominal skin (women 46.5 +/- 12.2 years old), obtained during plastic surgery. Intra- and interindividual variations are discussed on the basis of estimations of three acoustic parameters (slope of attenuation- beta; integrated attenuation coefficient- IAC; integrated backscattering coefficient- IBC) and one texture parameter (based on two estimators of effective density of scatterers: alpha(2) and alpha(1/2)) as a function of surface area and depth of acquisition in the frequency range 22 to 45 MHz. Values of intraindividual variations varied from 7.1% for IAC to 23.2% for IBC, and significantly decreased at a ratio between 1.2 to 2.3 when the acquisition surface area was increased from 4 mm(2) to 1 cm(2). Interindividual variations were higher than intraindividual variations, and varied from 14.2% for alpha(1/2) to 51% for IBC. The mean values (+/- SD) for all specimens combined, estimated with a large number of independent radiofrequency (RF) lines (400) and for a surface area of exploration of 4 cm(2), were 1.06 +/- 0.17 dB cm(-1) MHz(-1) for beta, 135 +/- 37 dB cm(-1) for IAC, (3.7 +/- 1.9) x 10(-2) cm(-1) sr(-1) for IBC, 1.40 +/- 0.17 scatterers/resolution cell for alpha(2) and 1.32 +/- 0.27 scatterers/resolution cell for alpha(1/2). Finally, attenuation micro(f) and backscattering coefficient sigma(b)(f) were compared to published results for the same parameters measured in human skin.