This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims to develop drug carriers that can both act as ultrasound contrast agents and therapeutic delivery vehicles activated by specific ultrasound pulses. These carriers must contain both a gas component for ultrasound contrast as well as a therapeutic molecule that retains its bioactivity once delivered to a target site. The carrier formulations under investigation are made primarily of lipids and inert gases for biocompatiblity. Challenges include incorporating an effective amount of therapeutic molecules without compromising contrast abilities. These challenges are being overcome through chemical conjugation of a therapeutic molecule to the lipids composing the microbubble shell. Intermediate goals include lipid-based particles that can release drug upon insonation but lack substantial contrast enhancing capabilities, such as liposomal formulations. Ensuring that the formulation is still capable of ultrasound contrast ehnacement as well as ultrasound destruction is an additional intermediate goal. To further multi-level targeting, various targeting ligands can also be conjugated to the microbubble shell. Initially, toxicity assays in cell culture are used in conjunction with fluorescence microscopy to determine intracellular uptake of both the drug and the lipid vehicle. Flow cytometry will also be employed to validate induction of apoptosis as opposed to cytostatic affects or necrosis.
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