Adsorption and Desorption of a Phospholipid from Single Microbubbles under Pulsed Ultrasound Irradiation for Ultrasound-Triggered Drug Delivery

Abstract

Microbubbles have potential for applications as drug and gene delivery systems in which the release of a substance is triggered by an ultrasonic pulse. In this paper, we discuss the adsorption and desorption of a film of phospholipid on the surface of a single microbubble under ultrasound irradiation. Our optical observation system consisted of a high-speed camera, a laser Doppler vibrometer, and an ultrasound cell; 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) was used as the surfactant. The adsorption of the DMPC molecules onto the surface of the bubble was evaluated by measuring the contact angle between the bubble and a glass plate. A decrease of the contact angle of the bubble indicates desorption of the DMPC molecules from the bubble surface into the surrounding aqueous solution. The amount of DMPC molecules adsorbed on the bubble's surface is shown to decrease over time after bubble generation. The type and intensity of the pulsed ultrasound waves were varied so as mimic ultrasound triggered drug release. Increasing the number of cycles and the amplitude of the sound pressure of the pulsed ultrasound yielded a greater increase of the contact angle. We also measured the radial vibrations of the microbubbles in the ultrasound field. The vibrational characteristics of the microbubbles and the desorption characteristics of the DMPC molecules showed the same variation; namely, a greater sound pressure amplitude induced greater vibrational displacement and a larger amount of molecular desorption under resonance conditions. These results support the possibility of controlling drug release with pulsed ultrasound in a microbubble-based drug delivery system.

Investigating the Role of Lipid Transfer in Microbubble-Mediated Drug Delivery

“…As stated above, sonication has a number of limitations, in particular, the relatively broad size distribution of the microbubbles produced and inefficient and/or nonuniform incorporation of coating components. Alternative methods include electrolytic, electrohydrodynamic, laser-based, gyratory, microfluidic, and hybrid approaches, although these still suffer from relatively low production rates. Unnikrishnan et al have also recently shown that amalgamation may provide a more efficient process for incorporating targeting species into microbubble coatings, and this might offer a superior method for producing lyso-MBs.…”

Generation of Monodisperse Microbubbles with a Controlled Size of Less Than 10 µm at a Generation Rate on the Order of 10⁵ Bubbles/s in Glass Capillary Microfluidic Devices

“…In addition, it is important that the size distribution is narrow (high monodispersity), which provides a uniform response, thereby resulting in improved image quality (Talu et al, 2007;Kaya et al, 2010;Lin et al, 2016). Microbubbles are also expected to be suitable drug delivery carriers (Dijkmans et al, 2004;Unger et al, 2004;Nakata et al, 2019). Microbubbles can be ruptured to release drugs in target locations using ultrasound irradiation.…”

Visualization of a Standing Lattice of Scattered Light on Spherical Water Droplets under an Acoustic Field Using Biogenic Microparticles

“…Numerous studies have focused on possible applications of acoustic waves for microto millimeter structures. For example, methods for altering the mechanical condition of microbubbles coated by lipid molecules have been investigated for improving drug delivery systems, 1 and vibration and shrinking at the surface of microbubbles with lipid membranes have been analyzed. 2,3 To target micromechanical conditions, various approaches have been applied for liquid phases.…”