Stabilizing ultrafine bubles used in drug loading

Abstract

In recent years, ultrasound-guided delivery of drug loaded on extremely small carriers has become one of the most conspicuous trends in improvement of drug delivery. Ultrasound has often been used in combination with bubbles with diameter smaller than sub-micron, referred as ultrafine bubbles, to amplify the biophysical effects of the ultrasonic field. It is thus becoming increasingly important to understand the factors affecting the formation and properties of ultrafine bubbles in order to use them as an effective material, especially for strict medical applications. This study investigates ultrafine bubbles formed in electrolytes solution incorporating with ultrasound for drug loading and release. The role of electrolytes in inhibition of bubble coalescence has been examined by a series of experiment on the coalescence behavior of bubbles in neat water in comparison with that in 154 mM sodium chloride solution after generation and during a three-day storage period. Since the electrolyte concentration under studied mimics the physiological salt concentration in human blood, the insights brought by our study will be of great significance in laying the foundation for the utilization of ultrafine gas bubbles in drug delivery. Our laser scattering and contact angle measurements showed that nanobubbles formed in neat water mostly vanished after one day of storage; while those formed in salt solution remained mostly stable during three days of storage. Additionally, successful encapsulation of quercetin to ultrafine bubbles has been observed. The release of bubble-loaded quercetin by application of the high frequency acoustic wave has also been tracked; the result indicated that under the influence of high frequency acoustic wave, the ultrafine bubbles vibrated and liberated the drug. Keywords: Ultrafine bubbles Electrolytes Drug loading Ultrasound