Investigation of Focused Ultrasound with Contrast Agent on Normal and Tumor Vascular Permeability in Mice
Date Issued
2008
Date
2008
Author(s)
Huang, Chi-Hsun
Abstract
In recent years, the development of drug delivery to the tumor has been greatly extended to achieve successful cancer chemotherapy by using various carrier systems targeted to the tumor. The purpose of the site-specific control of drug delivery is to increase the concentration in the target tissues and on the other hands, to minimize the side effects in normal tissues. In the aspect of chemotherapeutic drug delivery, due to the significant differences between normal blood vessels and tumor blood vessels, macromolecular drug carriers tend to deliver the drug to tumor tissues, however, there are lots of barriers on the way of delivery. It has been shown that through the combination of ultrasound contrast agent and ultrasound, we can improve drug delivery and by applying this method, the effects of extravasation of macromolecular drug carriers across the tumor blood vessels could be enhanced. We use dextran rhodamine as macromolecular drug carriers, together with two-photon microscope to observe the permeability of dextran in both the normal blood vessels and the tumor blood vessels in dorsal skin of mice in vivo. Besides, we also use focused ultrasound at the frequency of 1 MHz, the peak of negative pressure of 0.6 MPa, and the burst length of 10 ms, combining with ultrasound contrast agent to investigate their effects. Our results suggest that in normal blood vessels, there is no significant difference between exposure to ultrasound or not after injection of ultrasound contrast agent. On the other hand, it is significantly different when our samples are exposed to ultrasound after injection of ultrasound contrast agent in the tumor blood vessels. The accumulation of dextran outside the blood vessels is increased in the tumor blood vessels. Our long term goal is to find out the best parameter and technology to raise the permeability, to increase the amount of accumulation and to extend distance of penetration of macromolecular drug carriers in the tumor to optimize the effects of tumor drug delivery.
Subjects
Tumor blood vessel
Drug delivery
Focused ultrasound
Ultrasound contrast agent
Two-photon microscope
SDGs
Type
thesis
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