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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