Page 204 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

8.4 Ultrasonic-activated drug delivery 203

bioeffects with destruction of the endothelial cells lining the tumor vasculature and a
decrease in tumor vascularity [74].
Andrew K.W. Wood and Chandra M. Sehgal grouped the research studies
according to the type of cancer cell and the accompanying sonsensitizer that were
insonated; to provide a guide to previous sonodynamic studies in which the type of
cancer receiving therapy is emphasized [71].
To date the in vivo observations have been performed in implanted subcutaneous
tumors of laboratory animals so that there remains a need for future studies in a larger
mammal, perhaps using SDT for treating naturally occurring cancers.

8.4.3 Chemotherapy combination with ultrasound

In cancer therapy, there is interest in utilizing low-intensity ultrasound to enhance the
delivery of chemotherapeutic agents to a solid tumor. The agents do not selectively
target neoplastic cells and thus high levels of the cytotoxic drug in normal tissues
[71]. Insonation of a tumor in the presence of the chemotherapeutic agent provides
the potential for enhancing the delivery of the agent to the cancer cells whilst mini-
mizing the cytotoxic effects in the contiguous normal tissues.
Different approaches are used to study the ultrasound-mediated chemotherapy.
Drug delivery based on chemotherapeutic agents in combination with ultrasound are
improved with various techniques that introduced as follows.
8.4.3.1 Chemotherapy in presence of ultrasound (US + Chemo)
Several in vitro and in vivo studies are reported about the potential for low-intensity
ultrasound to increase the sensitivity of cancer cells to a chemotherapeutic agent. The
human myelomonocytic cells, human uterine carcinoma cells, a human tongue squa-
mous cell carcinoma, a murine lymphoma, murine ovarian cancers are investigated
2
[71]. The frequency and intensity are varied about 0.24–1 MHz and 0.01–7.84 W/cm .
Both continuous and pulsed waves are used.
8.4.3.2 Chemotherapy in presence of ultrasound and microbubbles
(US + Chemo + microbubbles)
Chemotherapy in the presence of microbubbles and ultrasound has the potential to
enhance the in vivo delivery of the agent to a tumor with minimum side effects in
normal tissues [75]. Watanabe et al. observed that the chemoeffect of cisplatin was
enhanced in the presence of ultrasound associated with collapsing and cavitating
microbubbles [76]. It should also be noted that the release of the chemotherapeutic
agent from the intravascular microbubbles will also impact on the blood vessels, kill-
ing the vessels and permitting the therapeutic agent to leave the vessel. The murine
colon carcinoma and murine, mammary carcinoma cells, human breast cancer cells,
and human myelogenous leukemia cell cancers are some of the several in vitro and
in vivo studies for chemotherapy in presence of ultrasound and microbubbles. The
2
frequency, intensity, and pressure are varied about 0.5–2.25 MHz, 0.5–4 W/cm , and
0.1–2 MPa. Both continuous and pulsed waves are used.