Optimization of Production of PLA Microbubble Ultrasound Contrast Agents for Hydroxycamptothecin Delivery

In this paper, ultrasound contrast agents based on a high molecular polymer-poly lactic acid (PLA) and loaded with hydroxycamptothecin (HCPT) were prepared by combining ultrasound method and a Shirasu porous glass (SPG) membrane emulsification technique. A special focus was on the optimization of production of HCPT-PLA microbubbles. Different factors, such as the power and the time of ultrasonic action, the ratio of inner aqueous phase against outer oil phase, and the concentration of PLA were evaluated, and the average size of HCPT-PLA microbubbles, the drug carrying efficiency, as well as the acoustically- triggered drug release at 3 kHz ultrasound were determined. The study showed that the HCPT-PLA microbubbles prepared using our optimized conditions, were sphere-like in shape with a mean diameter of 1-7 mum. The drug loading efficiency reached up to 56.48% In vitro, the drug release of HCPT-PLA microbubbles increased significantly at 3 kHz ultrasound for 30 s compared with that of ultrasound-free condition. In conclusion, the HCPT-PLA microbubbles has the characteristics desirable for an intravenously administered ultrasound contrast agent for further clinical use.