Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery

Abstract

Micron- to nanometer-sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes, are being developed for diagnostic imaging and ultrasound mediated drug/gene delivery. This review provides an overview of the current state of the art of the mathematical models of the acoustic behavior of ultrasound contrast microbubbles. We also present a review of the in vitro experimental characterization of the acoustic properties of microbubble based contrast agents undertaken in our laboratory. The hierarchical two-pronged approach of modeling contrast agents we developed is demonstrated for a lipid coated (Sonazoid™) and a polymer shelled (poly D-L-lactic acid) contrast microbubbles. The acoustic and drug release properties of the newly developed echogenic liposomes are discussed for their use as simultaneous imaging and drug/gene delivery agents. Although echogenicity is conclusively demonstrated in experiments, its physical mechanisms remain uncertain. Addressing questions raised here will accelerate further development and eventual clinical approval of these novel technologies.

Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells

“…This method allows the entrapment of air inside vesicles, enabling them to reflect ultrasound. Although the exact location of air has not been determined conclusively, there are reports of air being trapped in the hydrophobic part of shell or inside the aqueous interior [59]. …”

Impulse response method for characterization of echogenic liposomes

“…21 Previously published transmission electron microscopy images have shown liposomes on the order of 2 lm diameter 24 as well as vesicles in the nanometer size range that could not be resolved using the optical methods described here. 25,26 Atomic force microscopy 20 and fluorescence microscopy studies 26 also indicate a broad size distribution, with particle sizes ranging over three orders of magnitude from tens of nanometers to microns.…”

“…35 However, the shell thickness has not been directly measured for microscopic encapsulated gas bubbles and estimates based on the dynamic response of the microbubble only give information about the interfacial rheological properties of the microbubble (i.e., zero-thickness interface model). 20 Therefore the large variation in viscosity estimates could be due to the number of lipid layers surrounding the encapsulated microbubbles. 7 The resolution of the fluorescence images presented in Fig.…”

“…19 The exact location of the entrapped air pockets, morphology of the encapsulation, and amount of air in each carrier has not been fully ascertained. [19][20][21] The objective of the present study was to measure the damping due to the encapsulation and to estimate the shell viscosity based on the unforced response of individual ELIP exposed to a broadband acoustic impulse excitation.…”

Cell mechanics in biomedical cavitation

“…Liposome is an artificial cellular entity (a few micrometres in diameter) where a liquid drop or gas is closed by a lipid bilayer membrane (about 10 nm in thickness) and is often used as a model cell in biomechanical studies. Liposome has long been used as drug delivery vehicle by encapsulating drugs within the bilayer membrane since it exhibits excellent biocompatibility such as longer lifespan in blood circulation, low toxicity and easily taken up by targeted tissue [17]. Recently, ultrasonic cavitation has been applied to trigger or induce drug release from liposome [18] (figure 2).…”