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MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED DRUG DELIVERY. Doudou Xu PhD Student Institute for Medical Science and Technology (IMSaT) University of Dundee, Scotland. Outline. Introduction: Nanoporation Project Thermal Sensitive Sugar Based Carrier Nano-Sonication
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MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED DRUG DELIVERY Doudou Xu PhD Student Institute for Medical Science and Technology (IMSaT) University of Dundee, Scotland
Outline • Introduction: Nanoporation Project • Thermal Sensitive Sugar Based Carrier • Nano-Sonication • Conclusion • Future Study
Nanoporation Nanoporation is an interdisciplinary project • Pre-clinical oncology research • Cell biology • Magnetic Resonance guided Focused UltrasoundSurgery((MRgFUS) • Drug encapsulation nano-capsules • Targeted delivery of existing chemotherapy drugs • Nano-scale sonication research
MRgFUS- Magnetic Resonance guided Focused UltrasoundSurgery • MRgFUS combines High Intensity Focused Ultrasound, that ablates a targeted tissue (non-invasively) monitored by MRI HIFU treated turkey breast
The Nano-vehicles • Sugar based nanocarrier which can increase the solubility of hydrophobic drugs • The encapsulation is at molecular level • The carrier is triggered to release the drug at the tumor site Peptide Carrier Targeting group Encapsulated drug
Thermo-Sensitive Carrier (I) • Encapsulation percentage around 95%; • 40-fold more uptake at 80°C than 37°C for Doxorubicin encapsulated carrier solution; DI=I[carrier]0-I[carrier]x
Thermo-Sensitive Carrier (II) No Thermal Effect Thermal Effect Hyperthermia Release Drug Carrier • Hyperthermia increased penetration of Doxorubicin • Hyperthermia decreased binding constant and release Doxorubicin
Nano-SonicationDoxorubicin Uptake Test Fluorescence Digraph 592.05nm With US (23.42) No US (11.79) Excitation λ =485nm Emission λ =592.05nm Slit=10
Conclusion • Optimised carrier for Doxorubicin encapsulation efficiency is over 95% • CapsuTech sugar based carrier is sensitive to thermal effect • Hyperthermia mediated by sonication has been validated
Future Studies • In vitro Viability test of Nano-Sonication by encapsulated Doxorubicin • In vivo studies in mice using ExAblate to release Doxorubicin from Nano-Carrier. • Encapsulation of additional drugs (Taxol, Camptothecin, and more) • Polymer level encapsulation research
Our Team: Insightec, Ltd, Israel: Yoav Medan, D.Sc., Chief System Architect Alex Volovick, M.Sc, Scientist Osnat Dogadkin, M.Sc. Scientist Bjoern Gerold, PhD Student. Yelena Vachutinsky, PhD, scientist Capsutech, Ltd, Israel: Jallal Gnaim, PhD, CTO-Founder Fabian Arditti, PhD, R&D Manager, Dana Gurevich, PhD student. Doudou Xu, PhD student Nizar Mishael, CPO, Bus. Dev. Institute for Medical Science and Technology (IMSAT), and University of Dundee, UK: Prof. Andreas Melzer, MD, Director of IMSaT Prof. Sandy Cochran, PhD, Deputy Director Lijun Wang, PhD, Head of Biol.Lab Paul Prentice, PhD, Scientist Ritu Maliki, PhD, Post-Doc
Acknowledgement • This research, Nanoporation, is an FP7 funded Marie Curie Industry-Academia Partnerships Pathway project, my studies are currently fully supported by Nanoporation • Supervisors in University of Dundee: Prof. Andreas Melzer, Dr. Lijun Wang • Supervisors in CapsuTech: Dr. Jallal Gnaim, Dr. Fabian Arditti