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作者 Burke, Caitlin W
書名 Microbubbles and ultrasound: Targeted nanoparticle delivery and mechanical ablation
國際標準書號 9781124704647
book jacket
說明 137 p
附註 Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page:
Adviser: Richard Price
Thesis (Ph.D.)--University of Virginia, 2011
Ultrasound (US)-mediated microbubble (MB) destruction may be useful in the treatment of peripheral arterial disease (PAD) through the stimulation of therapeutic arteriogenesis and malignant brain tumors through chemotherapeutic drug delivery. Here, we tested whether targeted drug/gene bearing nanoparticle (NP) delivery can be facilitated by the US mediated destruction of MBs or "composite" delivery agents
We tested whether NP [∼125nm; poly(lactic-co-glycolic acid)] delivery to skeletal muscle and tumor can be improved by covalently linking them to microbubbles (MNCA). When targeted to the ischemic hindlimb, an animal model of PAD, 1hr post treatment, 7.2% of the injected dosage (ID)/g was observed in the treated tissue, a 1.9-fold increase over muscles treated with MBs co-administered with NPs and an 8.4-fold increase over non-treated muscles. When targeted to subcutaneous C6 Gliomas, 1 hr post treatment, 16.18% of the ID/g was observed in the treated tumor, a 4.9-fold increase over tumors treated with MBs co-administered with NPs and an 8.3-fold increase over non-treated tumors. The targeted delivery of 5-fluorouracil (5FU)-bearing controlled-release NPs to subcutaneous C6 Glioma using MNCAs resulted in marked tumor growth inhibition and prolonged survival
The ability of luciferase (LUC) bearing polyethylenimine (PEI) polyethylene-glycol (PEG) NPs to transfect skeletal muscle following US-MB mediated delivery was also tested. Treatment with PEG/PEI NPs, smaller MBs, and lower peak-negative-pressures increased transfection efficacy. However, due to MB loss during infusion and size dependent elimination rates in vivo, it is difficult to decipher the effects of MB size from the effects of MB concentration. US-MB mediated PEG/PEI also delivery yielded more uniform and robust gene expression as compared to intramuscular injection at the same PEG/PEI dosage
In many brain cancer applications we believe it may be desirable to perform targeted drug delivery in conjunction with non-thermal ablation of the tumor microcirculation. Here, the duty factor (DF) of 1MHz pulsed US applied to MB-perfused subcutaneous C6-glioma tumors was varied. Results demonstrate that tumor blood flow was significantly reduced immediately after treatment. Seven days after treatment, tumor necrosis and apoptosis were significantly increased in all groups, while treatment with DF=0.005 and DF=0.01 US inhibited tumor growth by 63% and 75%, respectively, compared to untreated tumors
School code: 0246
Host Item Dissertation Abstracts International 72-09B
主題 Engineering, Biomedical
Health Sciences, Radiology
0541
0574
Alt Author University of Virginia
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