Microbubbles materials

Particulate agents (especially gas-filled microbubble materials) are currently approached with caution by physicians, regulatory agencies and industry marketing, despite the fact that by 2001, perhaps up to 100,000 patients (a rough estimate) will have received ultrasound contrast agents with very few (mostly minor) side effects manifested. 

The interaction of ultrasound waves with microbubbles allows a drug (including genetic material for gene therapy [10]) to be released from the particles selectively at the desired insonified areas of the body, thus allowing targeted delivery of therapeutic agents. Currently, this approach is still far from clinical application. 

Fig. 3. A dry powder microbubble precursor agent particles of water-soluble material (e.g., galactose) are coated with a surfactant (e.g., palmitic acid). Air or other gas is located in the spaces between particles. When water is added and galactose rapidly dissolved, gas-filled spaces between particles become individual microbubbles dispersed in the aqueous phase...

While the microbubbles with an albumin shell were already in development, other groups of researchers investigated the use of surfactants or fipid-stabilized microbubble shells. Pluronic-stabifized renografin-air bubbles were prepared, but their storage stability was unsatisfactory. It required sonication shear mixing immediately prior to administration into experimental animals [18]. Other materials fared considerably better. A combination of a hydrophobic Span and... 

It is possible that microbubble shell may be shattered during the interaction with an ultrasound pulse. Indeed, drastic variation of microbubble size, up to several-fold in less than a microsecond, has been reported [33], with linear speeds of the wall motion of microbubble approaching hundreds of meters per second in certain conditions. At these rates, it is easy to shatter the materials that would otherwise flow under slow deformation conditions. In some cases (e.g., lipid monolayer shells, which are held together solely by the hydrophobic interaction of the adjacent molecules), after such shattering the re-formation of the shell maybe possible in other cases - e.g., with a solid crosslinked polymer or a denatured protein shells - the detached iceberg-like pieces of the microbubble shell coat would probably not re-form and anneal, and the acoustic response of microbubbles to the subsequent ultrasound pulses would be different [34]. 

The materials used for the construction of the microbubble shell have to be fully biocompatible. They are either natural products (human albumin in the denatured albumin shell of Albunex and Optison), synthetic versions of natural... 

In line with discussions included in previous sections, ultrasonic experiments carried out on fresh water by different investigators indicate that the stabilization of gas microbubbles, acting as gas nuclei for ultrasonic cavitation, is always attributable to the presence of surface-active substances in the water (ref. 15-17,25). As a starting point, one should consider that laboratory tests with various tap waters, distilled waters, and salt solutions have shown that no water sample was ever encountered that did not contain at least traces of surface-active material (ref. 46). Sirotyuk (ref. 25) estimates that the content of surface-active substances in ordinary distilled water amounts to 10 7 mole/liter, and in tap water it is 10"6 mole/liter or higher. These values indicate the appreciable content of such substances in both cases (ref. 122), although they differ by roughly an order of magnitude in absolute value. It is essentially impossible to completely remove... 

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