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206    CHAPTER 8  Ultrasound applications in cancer therapy




                         [71]. Several studies in in vivo and in vitro reported that gene therapy has been suc-
                         cessful transfection of genetic material resulting in apoptosis of cancer cells and
                         decreased tumor growth. In some cases, the genetic material and microbubbles were
                         injected separately into a tumor [85] or alternatively they were mixed and then added
                         to the tissue culture or injected into the tumor [71]. The transfection/transduction of
                         genetic material was usually accomplished using nonviral techniques in this method,
                         but using a virus as a carrier with microbubbles was successful too [85, 86]. The
                         nonviral techniques are more safer than viral vector, but has low transfection effi-
                         ciencies, however, microbubbles are good carriers of genes with a greater capacity
                         for antisense oligonucleotides, and fragment of DNA and even the entire chromo-
                         some [71]. Sporadic capillary rupture and increased vascular permeability, as well as
                         enhanced permeability of cell membranes may play a role in the observed efficacy
                         of therapy. Ultrasound-mediated gene transfection is provided a distinct advantage
                         over systemic cancer therapies for tumors with their associated effects on normal
                         tissues. The Melanoma, prostate, squamous cell carcinoma and breast cancers are
                         investigated [71]. The frequency, intensity, and acoustic pressures are varied about
                                                  2
                         0.021–2  MHz, 0.22–4.6 W/cm , and 0.12–2.1  MPa. Both continuous and pulsed
                         waves are used.

                         8.4.5  Transdermal drug delivery
                         Transdermal drug delivery (TDD) is the most painless and noninvasive delivery
                         route. In this approach, drug penetrates deep inside the epidermis and dermis apply-
                         ing topically to healthy skin [65]. TDD is the preferable route for vaccination, it
                         improves the bioavailability of the drug and in this method the toxic side effect are
                         minimized [87]. Drug delivery via skin using ultrasound is known as sonophoresis
                         or sometimes called as phonophoresis. Ultrasound increases the porosity of the skin
                         causing enhance TDD. The duty cycle of ultrasound, the distance of horn-to-skin,
                         treatment time, and the composition of the coupling medium are important factor in
                         the efficacy of sonophoresis. Sonophoresis increases the permeability of the skin by
                         thermal effects or by cavitation.


                         8.4.6  Cardiovascular disease
                         The microbubble-mediated ultrasound therapy has been studied as a possible tool for
                         cardiovascular diseases. Microbubble destruction provides an increase in local con-
                         centration of drug. It releases drug at that particular location and increases the perme-
                         ability of the biological barriers. Hence it is very useful in a gene or DNA delivery
                         as it eases the transfection process and are used as a delivery vehicle. Because of
                         the barriers present in the endothelium region, it is so difficult to deliver therapeu-
                         tics in the treatment of atherosclerosis and other cardiovascular diseases like rheu-
                         matic heart disease, cardiomyopathy, and congenital heart disease. Treatment in such
                         conditions contains stem cell repair of valve damage and ischemic myometrium,
                         ultrasound-mediated drug delivery through gene therapy, and nanoparticle assisted
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