Drug Delivery using Low Frequency Ultrasound Interactions of ultrasound with cells and tissues can be broadly classified into physical and biological effects. While physical effects include ultrasound-induced structural modifications of the cells and tissues (for example, permeabilization of cell membranes), biological effects include the response generated by cells and tissues due to the physical effects of ultrasound (for example, heat shock response). Both these effects are thought to be mediated by inertial cavitation, which refers to the rapid growth and collapse of gas bubbles. Using in vitro and intermediate models (reconstructed tissues), we seek to develop a multi-scale understanding of the effects of ultrasound on biological structures in the context of two specific applications, trans-cutaneous immunization (TCI) and chemotherapy. TCI offers an advantageous mode of immunization due to the unique ability of dermal
immune cells, especially Langerhans cells, to present antigens to the immune system.
Langerhans cells, upon activation, migrate to the regional lymph nodes and lead to the
generation of systemic and mucosal immune responses. However, simple topical application
of vaccines does not yield sufficient contact between the antigen and Langerhans cells to
generate an adequate immune response. Using tetanus toxoid as a model vaccine, we found
that low-frequency ultrasound enhances the immune response induced by topical application
of tetanus toxoid. The adjuvant effect of ultrasound is partly explained by the enhanced delivery
of tetanus toxoid into the skin after ultrasound application and partly by migration/activation We have also identified a novel application of ultrasound in chemotherapy. Current
techniques of cytotoxic chemotherapeutic agents target a narrow range of cancers and have
low specificity. We discovered that a short application of low-frequency ultrasound selectively |