Formulation and Development of UV Activated Polymer Microbubbles as Ultrasound Contrast Agents for Imaging and Drug Delivery

Microbubbles, as contrast agents and drug carriers, have been widely used for the ranostic applications with ultrasound technology over the past three decades. Research in microbubbles has undergone numerous improvements from a compositional perspective as researchers aim for enhanced targeted drug delivery. Microbubbles shells, which typically encapsulate a gaseous core, are conventionally classified into three type’s proteins, lipids, and polymers. Polylactic Acid (PLA) polymers are FDA approved and have proven to be one of the best biomaterials for fabricating drug delivery vehicles owing to its stability when introduced in vivo. When PLA is used to fabricate microbubbles, drugs of interest can be encapsulated into the polymer shells and can be released at the site with the application of ultrasound to achieve targeted drug delivery. But two limitations encountered with this microbubbles are a lack of controlled drug release upon triggering and elasticity of polymer shell in an ultrasound field. This research focuses on the development of novel Ultraviolet (UV) sensitive shape changeable polymer microbubbles to improve polymer shell properties. Fabrication of these microbubbles was done by modifying a double emulsification method. A UV sensitive shape changeable polymer, Azobenzene, has been used along with PLA to address the elasticity issue. This blend of two polymers present in the microbubble shell has resulted in structural changes like pores, cracks, and golf-ball like appearances, in response to UV light. These structural changes are indicative of a change in flexibility of otherwise stiff PLA microbubble shell. Scanning Electron Microscopy images show a clear structural difference in UV exposed microbubbles. UV-Vis Spectroscopy results show the optical properties of these microbubbles and confirm the activation of UV sensitive polymer present on the microbubble shell. The reported differences confirm the change in structure and lay the foundation for future work where acoustic properties of this novel polymer microbubbles tested for elasticity followed by testing of drug encapsulation and drug release profile for controlled delivery and cell toxicity testing for biocompatibility of the azobenzene.