Sonoporation, drug delivery, and gene therapy

Abstract

Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters such as acoustic pressure, pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles.

Cationic versus Neutral Microbubbles for Ultrasound-mediated Gene Delivery in Cancer

“…Click Beetle Luciferase and b-Galactosidase Reporter Plasmid Preparation A reporter plasmid encoding for red-shifted click beetle luciferase (CBLuc) driven by a cytomegalovirus promoter was used to evaluate ultrasound-mediated transfection efficiency in cell culture and in a and duration), the MBs used (eg, concentration, size, and composition), and the target tissue (19,20). A key factor in gene delivery efficiency is the concentration of genetic material at the site of sonoporation (10)(11)(12)21).…”

Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy monitoring

“…While the peak negative pressure used in the experiment could induce sonoporation, 35 it is not expected that enough mechanical disruption of the channel has occurred to transport microbubbles up to 1 cm into the phantom to cause cavitation 36 as seen in the TEA-PAM images. Nor is it expected that endogenously-nucleated cavitation is occurring in the phantom at 300 kPa, as this is well below the cavitation threshold of the phantom.…”

Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells

“…Because the kidneys receive approximately 25% of the cardiac output, a considerable number of MBs will enter the kidneys after intravenous or arterial injection. Thus, MBs are considered as a suitable vector for targeted drug or gene delivery to the diseased kidney (Deelman et al, 2010;Liang et al, 2010;Castle et al, 2013;Cao et al, 2016). Generally, there are two alternative approaches to US-assisted drug delivery.…”