CHAPTER 7: Targeted Delivery with Ultrasound Activated Nano-encapsulated Drugs
Published:02 Jan 2018
As a therapeutic modality, targeted drug delivery (TDD) allows an increase in medication dose at a treatment site while avoiding effects in the rest of the human body. TDD can be achieved with different types of delivery vehicles or carriers which encapsulate the free drug and release it only at the target location. Ultrasound-mediated therapeutic drug delivery (USmTDD) is one of various methods for local drug release and it can also influence cell permeability. Furthermore, combining it with magnetic resonance imaging (MRI) provides a controllable system for drug release and impact assessment. In this chapter, one approach to USmTDD is described. This involves the synthesis and assessment of a suitable, novel drug carrier, with the ultrasonic drug release evaluated in vitro using a clinical MRI-guided focused ultrasound surgery (MRgFUS) system. Human cancer cell lines were subjected to Focused Ultrasound (FUS) using the ExAblate 2000 system (InSightec, Haifa, Israel). The experiments were conducted in a specially designed research environment which was comprehensively evaluated to ensure both cell sterility and proper FUS propagation. Various sonication parameters were applied, in conjunction with a commercially available ultrasound contrast agent (USCA), to achieve maximal cellular uptake of doxorubicin (Dox) with minimal decrease in cell viability. In the work presented here, the carrier was a novel cyclodextrin (CD) based molecule that was synthesized, chemically evaluated, and investigated in vitro via two release mechanisms, heating and physical effects, that were differentiated through appropriate detailed experimental protocols.