mri guided focused ultrasound activated nano encapsulated targeted drug delivery

The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674

SMIT 14.Sep.2011 Doudou Xu [email protected]

MRI GUIDED FOCUSED ULTRASOUND MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED ACTIVATED NANO ENCAPSULATED

TARGETED DRUG DELIVERYTARGETED DRUG DELIVERY

Doudou XuPhD 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 Ultrasound

Surgery((MRgFUS) • Drug encapsulation nano-capsules • Targeted delivery of existing chemotherapy drugs• Nano-scale sonication research



MRgFUS- Magnetic Resonance guided Focused Ultrasound Surgery

• 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

Encapsulated drug

Targeting group



Thermo-Sensitive Carrier (I)

0.0000.0200.0400.0600.0800.1000.1200.1400.1600.1800.200

0 0.0001 0.0002 0.0003 0.0004 0.0005

DI

[Carrier], M

K-Binding

26°C

33°C

47°C

66.25°C

DI=I[carrier]0-I[carrier]x

• Encapsulation percentage around 95%;

• 40-fold more uptake at 80°C than 37°C for Doxorubicin encapsulated carrier solution;



Thermo-Sensitive Carrier (II)

• Hyperthermia increased penetration of Doxorubicin • Hyperthermia decreased binding constant and release Doxorubicin

No Thermal Effect Thermal Effect

Hyperthermia Release

Drug

Carrier



In vitro Sonication Machine (I)



In vitro Sonication Machine (II)



Nano-SonicationDoxorubicin Uptake Test

Excitation λ =485nm Emission λ =592.05nm Slit=10

592.05nm

With US (23.42)

No US (11.79)

Fluorescence Digraph



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



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.

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

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

Our Team:



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

mri guided focused ultrasound activated nano encapsulated targeted drug delivery

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