Drug and Gene Delivery using Sonoporation for Cardiovascular Disease



Fig. 18.1
The representative cascade of events involved in sonoporation for gene therapy is as follows. Externally applied acoustic energy disrupts the intravascular acoustic microspheres, generating transient porosity within the endothelial cell borders. ApoA-I plasmids enter the cells, resulting in expression of human ApoA-I messenger RNA with resultant generation of circulating human ApoA-I protein, and finally production of de novo serum HDL, White arrows indicate presence of human ApoA-I messenger RNA in treated rat liver



Similarly, confirmatory data was reported from China in which investigators produced a therapeutic effect of the scavenger receptor B type I (SRBI) gene. This serves as a receptor for HDL when delivered by combining cationic liposomal microbubbles (CLMs) and ultrasound in hypercholesterolemic rats (Liu et al. 2013). Researchers found delivery of the SRBI gene resulted in a significant decrease in circulating lipid levels. Much like the direct increase in HDL generation, as demonstrated by ApoA-I gene therapy, the up-regulation of HDL receptors in this study may exert a protective role in hypercholesterolemia.




18.6 Summary of CEUS for Cardiovascular Diagnostic and Therapeutic Applications


As an alternative to viral-mediated therapies, non-viral-mediated gene therapies provide a unique opportunity to advance the field through the use of acoustic microspheres. These serve as a non-invasive, monitoring systems coupled with the opportunity to provide a localized delivery method, without the associated risks of ionizing radiation or potential chromosomal insertion (mutagenesis). The ongoing work of the investigators from the University of Bergen have broken new ground with their report of the use of acoustic microspheres to both monitor and better deliver chemotherapy to patients suffering from pancreatic cancer (Kotopoulis et al. 2013). The dual approach to therapy has been realized and presents a propitious beginning. Due to the advent and improvement of this technology, the list of potential applications of drug UTMD (ultrasound-targeted microbubble destruction) – from small molecules to plasmid DNA – is seemingly limitless. To this end, CV microbubble drug delivery may encompass the three forms of intervention, including pre-event management; HDL regulation via gene therapy, and intra-event relief; vascular reperfusion by sonothrombolyis, and post-event maintenance; prevention of restenosis through siRNA silencing.

The CEUS migration from diagnostic to therapeutic applications has opened new horizons for the volumetric analyses of microvascular perfusion monitoring and therapeutic delivery of localized agents. The ongoing developments in this technology provide a platform for designer therapies useful in complex diseases. In addition, the concurrent advancement of acoustic hardware, software and “wetware” will accelerate this progress. Collaborations between academia, industry and pharma should begin to focus their efforts to further define the underlying mechanisms, as well as determine the most relevant technology applications. This coupling of investigations and optimization for acoustic sonoporation will provide an opportunity to advance the field of medicine (Castle et al. 2013). This will require forward–looking study design, which has the highest potential for translational success, as research advances from discovery through to early clinical trials. In doing so, the concept of using microspheres to safely and effectively administer therapy is rapidly becoming a reality.


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Jun 4, 2017 | Posted by in ULTRASONOGRAPHY | Comments Off on Drug and Gene Delivery using Sonoporation for Cardiovascular Disease

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