Ultrasound Sensitive Multilayer Emulsion Microbubbles Enclosing Biodegradable And Hollow Vaterite Nanospheres

Due to the systemic toxicity of therapies aimed at treating metastatic E-Wing’s sarcoma (ES), there is a need for an alternative drug delivery method that will increase patient survivability and quality of life. The achievement of a two-stage, more effective platform for biocompatible drug delivery is pursued with the design rationale of pharmacokinetic alteration through encapsulation in a drug reservoir of multiple nanospheres that are then immobilized in ultrasound sensitive microbubbles for targeted release. Coupling multilayered emulsion microbubbles with hollow, biodegradable vaterite nanospheres will make it possible for these two agents to coalesce into one functional delivery system, boosting overall selectivity, maximizing drug-loading capacity and increasing drug concentration at the cancerous region. The microbubble fabrication step resulted in a 3-layer construction consisting of an exterior polymer shell, an inner oil layer and a nitrogen gas core with a mean diameter of approximately 2 µm. Results from a variable depth study using a fixed ultrasound frequency, in which normal and cancerous cells are exposed to ultrasound for altering time durations, will demonstrate successful microbubble rupture and explain whether ultrasound intensity affects cell viability. Fabrication of vaterite nanospheres as the drug reservoirs followed existing procedures for synthesizing vaterite from water-induced phase transformation of poly(4-sodium styrene sulfonate)-stabilized calcium carbonate nanoparticles in a water-ethanol solution. The drug-loaded nanospheres will then be embedded, during the microbubble emulsion process, into the secondary microbubble layer to complete the foundation for the proposed drug delivery system.

Partially supported by TWD RISE GM60655.