Preparation of polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent

Objective: To prepare polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent (UCA) and evaluate its effects in contrast imaging on normal rabbit's liver parenchyma. Methods: Perfluorocarbon (PFC) -containing microbubble UCA (ST68-PFC) were prepared by sonication-based on surfactants (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polylysine (PLL) and alginate (Alg) by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in contrast imaging on normal rabbit's liver parenchyma were assessed. Results: The obtained microbubble UCA exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film-coated UCA effectively enhanced the imaging of rabbit's liver parenchyma. Conclusions: The novel microbubble UCA obtained via layer-by-layer self-assembly, when enabling more functions, has no obvious difference in enhancement effects compared with the premoditied microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for the attachment of targeting ligands to microbubbles, which allows the selective targeting of the microbubbles to desired sites.