Accelerating the Expansion of BCITs Innovation Capacity

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Accelerating the Expansion of BCITs Innovation
Capacity
NANOTECH BC BCIT Networking Session June 7,
2007 Ellen K. Wasan, Ph.D BCIT School of Health
Sciences
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BCIT a unique polytechnic institution

• Polytechnics are characterized by

• career-oriented training to meet long term
  economic development needs
• direct interaction with industry
• educational programming from trades certificates
  ? technology diplomas ? undergraduate and
  postgraduate degrees
• applied research aimed at increasing economic
  activity.

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BCITs mandate includes

• Engaging in technology transfer and contracted
  applied research

• focus on multi-disciplinary, collaborative,
  industry-relevant activities
• focus on business solutions through strategic use
  of relevant technologies
• build on existing strengths in key sectors and
  disciplines.
• Expand ability to work with industry to offer
  market relevant solutions such as
• Pre-Commercial Business Project Planning
• Prototype Development
• Technology Commercialization
• Research Workshops Seminars

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Demonstrating the Impact of Research in
Polytechnics
Creating impact is our business!

• Goal of polytechnic research is to enhance
  business outcomes by
• solving business problems
• implementing relevant technology strategies
• adopting appropriate technology
• improving clients products and methods
• identifying and avoiding downstream risks
• BCIT is actively looking at defining appropriate
  measures of its impact consistent with its
  polytechnic role in British Columbia

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Research Presentation Nanotechnology in Cancer
TherapeuticsApplication of Material Properties
to Solve Problems in Drug Delivery
Ellen K. Wasan, Ph.D Faculty, School of Health
Sciences, Basic Health Sciences Program,
BCIT Research Scientist, Dept. of Advanced
Therapeutics, BC Cancer Agency Adjunct Professor,
Faculty of Pharmaceutical Sciences, University of
British Columbia
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What are Nanopharmaceuticals?

• Example drug delivery systems Use of
  self-assembling materials that form a carrier for
  the active drug
• The carrier itself is a nanostructure (10-150nm)
• The way the body handles the drug is altered by
  its incorporation into the carrier and dependent
  on the particle size of the carrier
• Biodistribution
• Half-life in the blood
• Specific toxicities

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Nanopharmaceuticals in Cancer Treatment

• GoalGet the drug to sites of tumor growth
• Avoid specific, dose-limiting toxicities
• Conquer problems with drug solubility
• Alter the rate of elimination from the body

Photo from the University of Wisconsin
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Tumor Physiology and Nanopharmaceuticals

• Tumors have aberrant blood vessel and lymphatic
  structure and function
• Particles in the range of 100 nm can become
  selectively entrapped in tumor vasculature
• Lipid bilayer spheres (liposomes) can be made as
  100 nm vesicles encapsulating chemotherapeutic
  drugs for delivery to tumors

10-20 nm micelles
100-120 nm liposomes
Lipid bilayer
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Rational for the Use of Injectable Lipid
Nanopharmaceuticals in Cancer Treatment
Electron micrograph of liposomes
Blood Vessel
Tumor
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Novel Concepts in Drug Delivery with
Nanopharmaceuticals

• Example 1 Triggered release of a soluble drug
• Release on demand from the carrier
• Site-specific drug release
• Need rapid, complete release
• Need excellent retention prior to drug release
• at the desired site
• Example 2 Loading and retention of poorly water
  soluble drugs into liposomes

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Example 1 Triggered Drug Release Using Elevated
Temperature

• Phospholipid membranes display a gel to
  liquid-crystalline phase transition at a critical
  temperature Tc
• Liquid-crystalline phase has increased
  permeability? drug release

temperature gt Tc (chain melting)
e.g. localized mild heating of a specific tumor
region
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Nanopharmaceuticals Benchtop to Bedside
Imaging drug fate inside the tumors
Drug formulation in liposomes
Customizing drug release by heating pattern
Clinical applications
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Exploring the Role of Specific Carrier Components
(Lysolipid) on Drug Release Rate
37C
42C
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Novel Concepts in Drug Delivery with
Nanopharmaceuticals

• Example 2
• Loading and retention of poorly water soluble
  drugs into liposomes
• Many potential cancer therapeutics are difficult
  to dissolve, which limits the injectable dose
• Usually liposomes hold the water soluble drugs in
  the aqueous interior
• Typically, lipophilic drugs easily leave the
  lipid bilayer of the liposomes very quickly

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Example 2 Loading and retention of poorly water
soluble drugs into liposomes with the Micelle
Transfer Method platform technology
Pre-formed 100nm liposome
HydrophobicDrug
polymerized lipid
10-20nm micelle
Cogswell S, Berger S, Waterhouse D, Bally MB,
Wasan EK. A parenteral econazole formulation
using a novel micelle-to-liposome transfer
method in vitro characterization and tumor
growth delay in a breast cancer xenograft model.
Pharmaceutical Research 2006 Nov23(11)2575-85.
US Patent pending.
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Summary

• Small packets of drugs (nanopharmaceuticals) can
  be designed to behave in a predictable fashion
• Their properties are determined mainly by
• Physical and chemical properties of the drug load
  and the carrier components
• Molecular interactions between lipids composing
  structure (self-assembly)
• Particle size
• Research on the properties of nanomaterials will
  continue to give rise to new applications in drug
  delivery technology

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Acknowledgements

• Funding Canadian Institutes of Health Research,
  Cancer Research Society, John and Lottie Hecht
  Foundation
• Collaborators
• Singapore University Gigi N.C Chiu
• BC Cancer Agency Marcel Bally
• University of Toronto Stuart Berger
• University of British Columbia, Faculty of
  Pharmaceutical Sciences
• Duke University Mark Dewhirst
• British Columbia Institute of Technology
• Students and Research Assistants
• Sebastian Cogswell, Brian Banno, Jeffrey Gagnon,
  Zhao Wang, Rebecca Ng, Maryam Osooley, Dana
  Masin, Malathi Anantha, Allison Connor