Abstract:
Aqueous suspensions of microbubbles find use in various biomedical and pharmaceutical applications. Microbubbles of size from 1-10 μm, comprise of a gas core and a shell made of protein, SDS or polymeric material. Most of the biomedical applications involve intravenous administrations of microbubbles. Once administered in body, microbubbles start dissolving in the body media. The effectiveness of these microbubbles depends on their circulation time in blood. The circulation time (or persistence time) of these microbubbles largely depends upon the kinetics of their dissolution in body media. It is therefore necessary to know/predict the time for which the microbubbles made from a particular formulation will circulate in blood. Accordingly, the objectives of this work were to model microbubble dissolution and predict dissolution time.
There are several models available in the literature aimed at attempting the modeling of microbubble dissolution. However, it was found that, the existing models do not take into account either the shell elasticity or the variation in surface tension with change in microbubble size. In this work, attempt has been made to account for these factors which may affect microbubble dissolution process greatly.
The model for microbubble dissolution in an aqueous medium saturated with gas used to make microbubble has been developed. The values of shell resistance, elasticity and initial surface tension have been regressed by comparing model with the experimental data available I literature. It is found that, the shell resistance and elasticity of shell increases with number of carbon atom in lipids, thus dissolution time of the microbubble increases with number of carbon atoms in lipids. The dissolution time also increases with level of saturation and initial radius of the microbubble. As the Ostwald coefficient decreases, it is also observed that the dissolution time increases. The life time of gas with lower Ostwald coefficient microbubble is higher.
The degree of variations in shell resistance and surface tension also increases with number of carbon atom in lipid. However, based on the regressed shell properties, SDS can be considered as inelastic material as the variation in surface tension and shell resistance is negligible.
The model for dissolution of microbubble in multi gas environment in water and in blood has also been developed. Two way diffusion of core gas to the bulk and the diffusion of air dissolved in the bulk to the gas core have been considered. The growth in microbubble was observed during its dissolution due to higher influx of gases dissolved in the aqueous medium than outflux of gas used to make microbubble. The shell resistance of gases and surface tension of the microbubble first decreases and then increases. The dissolution time increases with number of carbon atom in a lipid molecule, initial radius and level of saturation of the aqueous medium.