Page 205 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

204 CHAPTER 8 Ultrasound applications in cancer therapy

8.4.3.3 Chemotherapy-loaded microbubbles and ultrasound
(US + Chemo loaded microbubbles)
The chemotherapeutic drug may be loaded or bound to a microbubble (diameter less
than an erythrocyte) [71]. On insonation of a tumor, ultrasound targeted microbubble
destruction occurs which has the advantages of being externally controlled and local-
ized to the tumor site. Tinkov et al. reviewed the formation of microbubbles and
their potential as carriers for drugs [34]. The structure of the shell of microbubble is
important; lipophilic chemotherapeutic drugs including doxorubicin, paclitaxel, and
docetaxel can be incorporated into the lipid layer of a microbubble [77]. The con-
cept of a theranostic microbubble which can combine a chemotherapeutic role with
ultrasound imaging is receiving increased attention [78]. The bubble is loaded with
a chemotherapeutic agent that is released in a tumor under the action of low-inten-
sity ultrasound; the bubbles may also act as a contrast agent and used for contrast-
enhanced power Doppler ultrasound imaging of the tumor vasculature. The breast
cancer cell and liver cancer in rabbits are two examples of research in this method
2
[72]. The frequency, intensity, and pressure are varied about 0.3–5 MHz, 1–3 W/cm ,
and 0.45–1.2 MPa. Only pulsed waves are used.
8.4.3.4 Chemotherapy-loaded polymeric micelles or liposomes and
ultrasound (US + Chemo loaded micelles)
The chemotherapy-loaded polymeric micelles or liposomes is another approach to
cancer therapy, that the agent release from the micelle under the action of ultrasound.
This method has been used to improve the delivery of chemotherapeutic drugs to a
tumor. Staples et al. suggested that cavitation events may have released the doxoru-
bicin from circulating and extravasated micelles into the tumor and insonation could
have transiently increased the permeability of the tumor neovasculature [79]. The
“shockwave ruptured nanopayload carriers” was developed by Ibsen et al. to mini-
mize the potential side effects a chemotherapeutic agent on normal tissues [80]. The
microbubble was encapsulated with a protective outer liposome. The subcutaneous
tumor, mice with a subcutaneous breast tumor and a subcutaneous colorectal epi-
thelial cancer cell line in rats are examples of research in this method [71]. The fre-
2
quency, intensity, and pressure are varied about 0.029–2.25 MHz, 1–5.9 W/cm , and
0.173–1.9 MPa. Both continuous and pulsed waves are used.
8.4.3.5 Chemotherapy-loaded liposomes in presence of ultrasound and
microbubbles (US + Chemo loaded micelles + microbubbles)
The intracellular absorption of a chemotherapeutic agent is enhanced by inertial
cavitation that induced by the insonation of microbubbles, in the other word absorp-
tion of ultrasound energy was enhanced by the oscillation and cavitation of micro-
bubbles within the insonated tumor. An intratumoral injection of microbubbles and
the intravenous injection of doxorubicin-loaded liposomes was applied by Zhao et al
[81]. They found that that cavitation was an important bioeffect of insonation and
enhanced the absorption of doxorubicin and the growth of breast cancer tumor in
mice was reduced. The mice breast cancer and a murine colorectal adenocarcinoma