**1. Introduction**

The recent advanced methods of noninvasive delivery of therapeutic agents are effective in gene therapy and molecular biology. Besides the well-known application of microbubbles have been demonstrated an effective technique for targeted delivery of drugs and genes and is also used as contrast agents for diagnostic ultrasound [1–6]. A schematic structure of the biomedical microbubble is shown in **Figure 1**. The size of microbubbles is larger than micrometer but smaller than one hundredth of millimeter in diameter which is equal to the size of red blood cell. Because of its smaller size, it can pass in the microvessels and capillaries throughout the body. In aqueous environment, the microbubbles are unstable and show surface tension effect because of this properly it require the shell and filling material. The gas core of microbubbles gets stabilized by lipid, protein, and polymers [7, 8]. In water microbubbles are miniature gas bubbles of less than 50 microns diameter.

#### **Figure 1.**

*Illustration describe various shell compositions of microbubbles. The diameter between 0.5 and 10 μm is applied for biomedical use so that it can pass through the capillary of the lung. Microbubbles compose of total particle volume which act as single chamber so that the shell of the microbubble separate encapsulated gas and the surrounding aqueous medium by using various shell materials like lipid with thickness~3 nm thick, protein having 15–20 nm thick and polymer of 100–200 nm thick. Hydrophobic and Vander Waals interactions binds the lipid molecule together and by covalent disulphide bonding the protein molecules get cross-linked so that the formation of bulk like material.*

It mostly contains oxygen or air and remains suspended in the water for an extended period. The gas present in the microbubbles dissolves into the water, and the bubble disappears. Incorporation of drug in microbubble includes (1) binding of drug to microbubble shell and (2) attachment of drug at specific site of ligand. In ultrasound-mediated microbubbles, application of high intensity ultra sound can rupture capillary blood vessels resulting in deposit of protein and genetic material into the tissue, ultrasonic rupture of microvessels with diameter 7 μm. Ultrasound forms pores in the membrane of shell. Ultrasound microbubble causes transient hole in the cell surface resulting in rapid translocation of plasmid DNA from the outside to cytoplasm. Low-intensity ultrasound microbubble (0.6 W/cm<sup>2</sup> ) caused enhanced drug delivery [55]. Microbubbles are usually injected intravenously which is a safe process as compared to the use of conventional method like magnetic resonance imaging and radiography. Microbubble is used in the medical field as diagnostic aids to scan the various organs of the body, and recently they are being proposed to be used as drug or gene carriers and also for treatment in cancer therapy. It is also used to improve the fermentation of soil, to increase the hydroponic plant growth, to increase the aquaculture productivity, and to improve the quality of water, in sewage treatment.
