Phospholipid-based ultrasonic microbubbles for loading protein and ultrasound-triggered release

Abstract

Background: Ultrasonic microbubbles are used as ultrasound-triggered delivery carriers for protein drugs. Aim: This work was to prepare stabilized protein-loaded phospholipid-based ultrasonic microbubbles (PUM) and to determine its value as a protein delivery system. Method: Bovine serum albumin (BSA) was used as a model protein drug. BSA-containing PUM were prepared by dissolving lyophilized PUM powder in BSA solution. The particle size and microbubble concentration of BSA-containing PUM were measured. The BSA encapsulation efficiency as a function of BSA concentration was determined. Contrast enhancement of BSA-containing PUM in vivo was detected. The release profile of BSA from PUM was also investigated. Results: The mean particle size and microbubble concentration of PUM were unchanged by the presence of BSA for at least 30 minutes after preparation. The net amount of BSA entrapped in PUM was maintained unchanged with increasing BSA concentration. BSA-containing PUM were shown easily to be visible in in vivo rabbit kidney. There was no difference in echogenicity between the loaded and unloaded PUM. Ultrasound duration had a positive relationship with BSA release. Ultrasound of 30 seconds stimulated 94.1% and 93.3% of BSA release from PUM solutions containing 0.3% and 1.5% BSA, respectively. Conclusions: Protein-loaded PUM exhibited satisfactory physical characteristics and were potent for using in ultrasound-triggered delivery.

Keywords:

• BSA
• loading efficiency
• microbubbles
• ultrasound
• ultrasound-triggered release

Acknowledgments

The work of Ying-Zheng Zhao is supported by the National Natural Science Funds (30870755), medicine and health grants from Wenzhou Bureau of Science and Technology (Y20080098), and development funds from Wenzhou Medical College (QTJ08001).

Declaration of interest: The authors report no conflicts of interest.