Аннотация:Microbubbles are routinely used ultrasound contrast agents in the clinic. While a soft protein shell is commercially preferable for imaging purposes, a rigid polymer shell demonstratesprolonged agent stability. Hence, combining polymers and proteinsin one shell composition can advance microbubble properties. Weformulated the hybrid “protein−copolymer” microbubble shellwith a complex of bovine serum albumin and an amphiphiliccopolymer of N-vinyl-2-pyrrolidone and acrylic acid. The resultingmicrobubbles demonstrated advanced physicochemical andacoustic properties, preserving in vitro biocompatibility. Adjustingthe mass ratio between protein and copolymer allowed fine tuningof the microbubble properties of concentration (by two orders, upto 1010 MBs/mL), mean size (from 0.8 to 5 μm), and shellthickness (from 28 to 50 nm). In addition, the minimum air−liquidsurface tension for the “protein−copolymer” solution enabled the highest bubble concentration. At the same time, a higher copolymer amount in the bubble shell increased the bubble size and tuned duration and intensity of the contrast during an ultrasound procedure. Demonstrated results exemplify the potential of the hybrid “protein−polymer” microbubble shell, allowing tailoring of microbubble properties for image-guided applications, combining advances of each material involved in the formulation.KEYWORDS: microbubbles, ultrasound, N-vinyl-2-pyrrolidone, bovine serum albumin, polymers, proteins, contrast agents