The effect of glucosamine on the acoustic and binding properties of albumin-based microbubbles (work in progress)

Cationic lipid microbubbles have been shown to load DNA and improve transfection by ultrasound. Protein based microbubbles, which typically have higher transfection ability than lipid-based, have also been made to load DNA but have not been fully trialled in vivo. Glucosamine (GlcA) is a positively charged sugar which could potentially produce a DNA-loading albumin microbubble. Microbubbles were made with 2% (w/v) albumin, octafluoropropane and 55% (w/v) dextrose or 40% (w/v) dextrose and 15% (w/v) GlcA, yielding two bubble types. These were acoustically characterised and their DNA-loading ability was examined. Preliminary in vivo work investigated their effectiveness at transfecting CD1 mice hearts with a luciferase plasmid (pGL4.13) using ultrasound. The two formulations produced microbubbles of similar concentration and size distribution. Bulk acoustic behaviour was also similar, with GlcA microbubbles displaying greater attenuation behaviour. GlcA microbubbles were found to be capable of loading a significantly more plasmid DNA compared to the control bubble; however no difference in transfection ability was noted. DNA-loading albumin microbubbles can be simply made by the addition of GlcA and the produced microbubbles are well-tolerated by mice with no adverse events observed. On-going work will determine the effect of microbubble DNA-loading on ultrasound and microbubble mediated gene transfection (UMGT).