Page 202 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

8.4 Ultrasonic-activated drug delivery 201

8.4.1 Drug carriers for ultrasound drug delivery
8.4.1.1 Liposomes
Liposome, the most biocompatible nanocarriers that are used for targeted drug
delivery, overcome the obstacles of cellular uptake and cause increasing the bio-
availability and biodistribution of the compound at the targeted site. Liposomes
are self-assembled bilayer phospholipids produced at the temperature above the
transition temperature of the lipid by hydration of dry phospholipids in the aque-
ous medium. Liposome enables to carry both hydrophilic and hydrophobic com-
pounds. Because of this unique property, liposomes are widely used for delivery of
chemotherapeutic agents, DNA, proteins, enzymes, etc. [65]. For the development
of ligand-targeted liposomes, liposomes are coupled with some functionally active
compounds to deliver the therapeutic agent in addition to detect the treatment grade
[66]. The drug is loaded in a conjugated form or encapsulated form in liposome. Due
to the fact that liposomes reduce the drug toxicity and increase the drug specificity,
are known as excellent carriers.

8.4.1.2 Micelles
Micelles consist of polymeric core-shell structures synthesized from amphiphilic
block copolymers. Advantages of micelles over other nanocarriers like liposomes are
that obtaining liposomes less than 50 nm is difficult and complex [67]. Due to being
single-layer structures, the core of the micelles stays hydrophobic, enabling entrap-
ment of poorly soluble drugs in the core of micelles. Also, this feature increases the
solubility, improving the bioavailability and circulation time of drugs. High drug
loading capacity causes micelles are used for targeted drug delivery [65]. Also, opso-
nization of micelles with sugar or peptide can result in receptor-mediated targeted
drug or gene delivery. Micelles are classified into three categories; self-assembled
micelles, unimolecular micelles, and cross-linked micelles.

8.4.1.3 Microbubbles
Microbubbles are gas bubbles ranging between 1 and 8 µm wrapped with protein,
peptides, polymer, drugs, etc. Ultrasound imaging and ultrasound-based drug deliv-
ery use microbubbles as a contrast agent [34]. Cavitation of microbubbles generates
temporary or permanent pores in the blood vessel membrane that increases extra-
vascular delivery of therapeutic compounds to the target organ. Sonoporation allows
the delivery of therapeutic compounds without compromising cells’ physiological
barriers and the defense mechanisms of the cells [65]. As the pores created during
sonoporation are temporary, and they usually return to their original confirmation
within a few seconds, it is known to be a safe method.
8.4.1.4 Microspheres
Microspheres are polymeric particles ranging from 1 to 1000 µm [65]. Drug
can be encapsulated or entrapped form in microsphere in order to drug delivery.
Microspheres are used for targeted as well as long-term drug release in the diseased