Thanks to modern research methods, the existence of nanobubbles in various environments has become an indisputable fact. The scope of their application is expanding: from agriculture and wastewater treatment to manufacturing and medicine. We have already given a general description of nanobubbles here. This review presents new data from studies of nanobubbles.
As far as the study of bulk nanobubble structure is concerned, gaps remain. In particular, we are referring to their stability in water. Boris Boshenyatov concludes that the stability of nanobubbles is thanks to their low concentration and reduced surface tension at the gas-water phase interface, which is in turn due to adsorption of impurities on the surface of the bubbles. Stability may also be connected with the perculiarities of the nanobubble shell's construction, namely, the presence of a double electric layer. At the same time, Song-Nam Hong used computer modelling to calculate the maximum distance between nanobubbles that would ensure their stability. According to the author, it should be equal to the radius of the nanobubble to the power of 0.75.
According to the classical theory of diffusion, bulk nanobubbles should not exist in a solution for more than a few microseconds, however scientists have observed them for periods of up to several days. According to the results published by the Polish scientist Karol Ulatowski, nanobubbles can remain stable for even a month. Ulatovsky created them by passing water through porous membranes. He noted that nanobubbles do not dissolve in a liquid and do not merge with each other. The stability and size of the nanobubbles did not depend on whether the samples being studied were open to external influences or not.
Another unresolved question is whether OH radicals are formed from oxygen-containing nanobubbles in water without ultrasonic action or pressure changes. The Japanese scientist Kyuichi Yasui used mathematical modelling to show that for every 107 nanobubbles, several OH radicals can form in the aqueous phase without external dynamic stimuli. Yasui came to such a conclusion based on the temperature (2800 K) and pressure (4.5 GPa) calculated inside the oxygen bubble at the point of dissolution.
Computer model of nanobubble formation in water before (A) and after (B) the change in sample volume.
The American scientist Sa Hoon Min combined experimental results with computer simulation results obtained in 2005 by the TIP4P water model to reveal the main characteristics of nanobubbles and confirm the results of previous studies. The author also concluded that nanobubbles form when 'stretching' small volumes of water. This observation may be important in understanding the processes occurring in biological tissues after various injuries. It is possible that with an injury there is a sharp 'stretching' of the volume of water with the formation of nanobubbles. These nanobubbles may cause damage to nearby cells.
Echogenic images of NanoBubbles visualised using sonography (Esaote, Genova, Italy)
Part of modern research is devoted to the applying the concept of nanobubbles in order to obtain new forms of drug administration. Thus, according to the Italian scientist Federica Bessone, nanobubbles can act as an innovative tool to increase the level of specificity of a drug in relation to certain cells, which in turn leads to an increase in the efficacy of therapy, as well as a decrease in the severity of its side effects. The Bessone research team is engaged in the research and development of dextran-coated nanobubbles with curcumin extract inside. Such systems are effective in the treatment of cancer for several reasons: the drug maintains its efficacy despite the significantly decreased concentration; it can be delivered directly to target organs and tissues; and it has 'echogenicity' - the ability to observe nanobubbles with ultrasound methods.
The use of ultrasound not only allows nanobubbles to be tracked, but also their movement in body tissues can be influenced. According to the Chinese scientist Xiaoying Zhou, ultrasound-driven drug delivery using nanobubbles is a promising strategy. The scientist successfully synthesised biocompatible chitosan nanobubbles loaded with the drug doxorubicin. The results of in vitro studies showed the efficacy of this approach.
The Australian scientist Sachin Thakur offers a similar strategy for drug delivery using nanobubbles, but for the treatment of eye diseases. Over the course of the study, the author optimised the nanobubic drug system on two independent models of the eye ex vivo, and studied the effect of ultrasound on the efficacy of such therapy. Studies have shown that ultrasound exposure accelerates the movement of the nanobubble sample injected into the posterior parts of the eyeball without causing damage to organ tissues. The author also noted that by applying ultrasound in different places, it is possible to change the direction of nanobubble migration.
The Korean scientist Khan investigated the influence of shell composition on size, distribution and other characteristics of oxygen-containing nanobubbles. In addition, the author discovered that such bubbles are non-toxic and that their use does not lead to hemolysis (destruction of red blood cells) for sheep blood.
pH-driven release of oxygen from nanobubbles in an acidic medium.
The Chinese scientist Ruyuan Song suggested using oxygen-containing nanobubbles to deliver oxygen to malignant tumours. Hypoxia (oxygen deficiency) is one of the important factors of a tumor's immunity to therapy. The author has developed oxygen-containing nanobubbles with a dextran shell, which release oxygen in response to a slight decrease in pH. In vivo experiments showed that the oxygen level inside a tumor exposed to dextran-coated oxygen-containing nanobubbles increased about six times compared to its initial level. Thus, oxygen delivery using pH-sensitive nanobubbles could be a breakthrough in the treatment of malignant tumours.
The findings show that the use of nanobubbles is promising in a variety of scientific fields, including obtaining effective next-generation drugs.