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CANADIAN RESEARCH FOCUS

Interview with Dr. Helen M. Burt

“The use of nanocrystalline cellulose for the binding and controlled release of drugs”, International Journal of Nanomedicine (2011).

6:321-330.

September 2nd, 2011

conducted by Patricia Comeau

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Presentation Contents

Brief background on article Slides 3 - 4 Interview with Dr. Burt Slides 5 - 18 Dr. Burt’s Biography Slides 19 - 21

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Nanocrystalline Cellulose (NCC) for Drug Delivery

• To date this use of cellulose has not involved a direct molecular level control of drug release by manipulating binding interactions with the drug.

• However, the large surface area and negative surface charge of nanocrystalline cellulose (NCC) suggests that provided large amount of drugs can be bound to the material’s surface, there is great potential for high payloads and optimal control of dosing.

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• The hydroxyl groups on NCC also provide an opportunity for surface modification by a variety of chemical groups for altering the loading and release of drugs.

• As NCC is a low-cost, readily abundant material it offers a substantial environmental advantage compared with other nanomaterials.

• In this article Dr. Burt and her research team investigate the binding and release of drugs from NCC with and without surface modification by cetyl trimethylammonium bromide (CTAB).

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Interview with Dr. Burt

Faculty of Pharmaceutical Sciences, University of

British Columbia

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What are the key target diseases for your NCC drug delivery system?

This remains to be determined, but we believe there are significant opportunities to explore the pharmaceutical applications of NCC as a drug delivery excipient either alone, or in conjunction with other formulations. For example, it may have applications in topical or mucosal controlled delivery of drugs; such as release of anti-infective agents from hydrocolloid wound dressings.

…continued on next slide →

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We are also suggesting that NCC may be

suitable for implantation into surgical resection

voids such as tumor sites, bone or periodontal

cavities. Alternatively, it may find application as

a component of controlled release oral

formulations.

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How does the surface charge of the NCC assist in the delivery of

hydrophobic or hydrophilic drugs?

We believe that the two ionized, hydrophilic drugs we studied probably bound by an ionic interaction with the negatively charged surface of NCC and that release occurred via an ion exchange mechanism, with the phosphate buffered saline release medium providing ions for exchange.

…continued on next slide →

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In the case of the hydrophobic drugs, the NCC

was coated with the cationic surfactant CTAB

and we believe the hydrophobic drugs

partitioned into the hydrophobic domains of the

CTAB. The release mechanism was likely due to

diffusion of the drugs out of the hydrophobic

domains of the CTAB-NCC.

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Are there any concerns with using cellulose from softwood in humans?

How efficient is the processing?

My colleague and co-author, Dr Wadood Hamad (FPInnovations) has expertise in this area and one of his publications reports that NCC with high crystallinity can be produced from commercial softwood pulp with yields of between 21-38%. Studies are ongoing to examine the extraction of NCC and potential environmental and toxicity issues.

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How does NaCl assist in flocculating NC and why is this a concern in your

synthesis of the NCC system?

NCC samples were provided to us as a stable colloidal dispersion in water and we needed to be able to centrifuge down the NCC particles. However, the NCC dispersion could not be sedimented under high speed centrifugation. The addition of PBS or 5 mM NaCl allowed for flocculation and enabled us to centrifuge the particles.

…continued on next slide →

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The NaCl is functioning as a flocculating electrolyte by reducing the zeta potential and hence the diffuse layer thickness of the electric double layer associated with NCC particles. The particles then form loosely bound flocculated particles held together by weak Van der Waal’s forces of attraction.

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What happens if you add too much NaCl?

Theoretically, the addition of excess electrolyte can sometimes result in deflocculation of the particles but this was not a problem in our work.

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What is your goal delivery duration?

There is a lot of work remaining to be done to

optimize the release from this system. At this

stage, we don’t have a particular release lifetime

as our goal. We would like to use different

surfactants bound to the surface or conjugate

short chain hydrophobic polymers onto the NCC

surface to bind drugs.

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Are there sites on the NCC which are more prone to drug binding/interaction?

This is probably explained by the different

modes of drug binding to the surface and

different release mechanisms between ionized,

hydrophilic drugs and hydrophobic drugs..

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How will the NCC system be administered into the body?

This work is still very early stage. I anticipate

that the first drug delivery applications might be

topical/mucosal.

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What major hurdles remain to be overcome in this technology before

clinical application?

There’s a lot we still need to learn about this technology and its potential for drug delivery applications. Studies are needed on; biocompatibility, the nature and range of drugs that can be bound to and released from NCC, understanding the factors influencing drug release rates, determining local delivery and disease sites with the best potential for the technology, to name but a few.

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CC-CRS Question #8

Thank you for the interview!

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Dr. Helen M. Burt

Biography of

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Dr Burt is the Angiotech Professor of Drug Delivery in the

Faculty of Pharmaceutical Sciences at UBC and since

September 2011, is the Associate Vice President,

Research & International. She was born in Manchester,

England and obtained her B. Pharm.(Hons) from the

University of Bath and her Ph.D in Pharmaceutics from

UBC.

Her major research efforts are supported by grants from

CIHR and NSERC and involve the development of

polymer-based drug delivery systems for controlled and

localized drug delivery. She has published over 140 peer-

reviewed papers and 8 patents. …continued on next slide →

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She has been the recipient of several teaching prizes and

research awards, including the UBC Killam Teaching Prize

and Killam Faculty Research Prize, NSERC Synergy Award

for Innovation, CSPS Award of Leadership in Canadian

Pharmaceutical Sciences and YWCA Woman of Distinction

Award for Science, Research and Technology.

She is a founding scientist in the Centre for Drug Research

and Development (CDRD), a member of the Canadian

Academy of Health Sciences and has served on the Board

of Directors of the Provincial Health Services Authority.