Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘drug delivery’

At the recent ARVO meeting, one of the symposia that I live tweeted from was on “Nanotechnology for Drug and Gene Delivery.”  During his presentation on “Nanomedicines: From Bench to Bedside” Vladimir Torchilin from Northeastern described how nanotechnology can use methods from other scientific disciplines including layer-by-layer (LbL) polymer chemistry.

Which leads me into an interesting paper that came across my desk from Zhiyong Poon and colleagues at the Koch Institute for Integrative Cancer Research at MIT.

In their paper published online on April 23, 2011 in ACS Nano. they describe how nanoparticles with a pH-sheddable layer can be used to target tumor hypoxia.

In other words, the nanoparticle can travel in the blood to the tumor, then in the changed acidity and pH of the tumor microenvironment, the outer stealth layer is eroded and shedded, exposing another layer of the nanoparticle that delivers drug to the target hypoxic tumor region.

Image Source:  ACS Nano. The author’s conclusion is that “this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.”

This proof of principle research is further progress towards the development of nanomedicines in oncology.

ResearchBlogging.orgPoon, Z., Chang, D., Zhao, X., & Hammond, P. (2011). Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for Targeting of Tumor Hypoxia ACS Nano DOI: 10.1021/nn200876f

Faced with the opportunity to read around 900+ posters yesterday afternoon in the first of the six main poster sessions from Sunday to Wednesday here at the AACR annual meeting, any selection of a “poster of the day” is extremely subjective.  All the posters here have considerable scientific merit having passed a rigorous peer-review selection process.

Faced with a smorgasboard of choice, one ends up focusing on areas of personal interest. One area I have recently started to write about on this blog is the impact nanotechnology may have on cancer research and in particular how nanoparticles in the form of diamonds can be used to reach into tumors.

So “my poster of the day” from Sunday April 3rd, Day 2 of AACR is  “Multistate Nanoparticle Delivery System for Deep Penetration into Tumor Tissue.” It is Abstract#548 on the AACR website, and is from a team of researchers at the Department of Chemistry at MIT, Massachusetts General Hospital and Harvard Medical School.

The published poster by Cliff Wong and colleagues is “a proof-of-principle demonstration that a size changing nanoparticle can facilitate delivery into the dense collagen matrix of a tumor.

The authors conclude, that what they have developed is: “the potential for customized delivery of nanoparticles by using genomic and molecular data to achieve optimal delivery for a particular patient.”

Heralding the future potential of their research, the poster states that as result of this work they now can “design a series of customized nanoparticles that are activated by a variety of tumor-associated proteases such as cathepsin B and urokinase plasminogen activator (uPA).

One question that this research raises to me is to what extent different tumors may require a different sized nanoparticles to deliver drug to the target area? If we do need different sized nanoparticles, then how do we determine which is the best size/combination?

I’m excited at the possibility that not only may we have personalized medicine, but that nanotechnology may enable customized drug delivery.

The heart of the AACR annual meeting to me is the posters, and they frequently stimulate questions that may generate novel new approaches or trigger new research avenues or opportunities to make a difference in the lives of future cancer patients.

 

Nanotechnology is set to have a major impact on drug development and new products for the diagnosis and treatment of cancer.  Research from UCSF and Northwestern University published earlier this year in “Science Translational Medicine” shows this potential.

Edward Chow and colleagues describe how binding the cancer chemotherapy doxorubicin (DOX) to carbon nanoparticles 2-8nm in diameter in the form of a diamond, “nanodiamond” (ND), improved drug efficacy and overcame drug resistance.  Although this pre-clinical animal research has not yet been confirmed in humans, it raises the possibility of more efficient chemotherapies and the hope of increased survival rates as a result.

The conclusion from this research is that nanodiamonds may be a viable drug delivery platform for small molecules, proteins and nucleic acids. This technology could have an application in wide range of diseases.

Why is nanoparticle-mediated drug delivery more effective? The paper suggests one reason is that the nanodiamond-doxorubicin complex (NDX) allows for a more gradual release of DOX, allowing for increased tumor retention and increased circulation time.

It’s important to note that the NDX complex does not specifically target the drug efflux pumps, such as MDR1 and ABCG2 transporter proteins, responsible for chemoresistance. Instead the NDX complex appears to overcome drug resistance passively by the way DOX is released from the nanodiamond.

This research shows that taking old drugs and combining them with new drug delivery technology may offer therapeutic benefits.  The authors conclude that this research, “serves as a promising foundation for continued NDX development and potential clinical application.”

If successful in humans, it will translate into new product development and market opportunities for emerging biotechnology and biopharmaceutical companies.

 

ResearchBlogging.orgChow, E., Zhang, X., Chen, M., Lam, R., Robinson, E., Huang, H., Schaffer, D., Osawa, E., Goga, A., & Ho, D. (2011). Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment Science Translational Medicine, 3 (73), 73-73 DOI: 10.1126/scitranslmed.3001713

Innovation in drug delivery presents opportunities for biotechnology companies, and is an area I expect we will see major leaps forward through nanotechnology.

Nanotechnology is the application of science and engineering to materials that are between 1 and 100 nanometers (nm) in size.  The Environment Protection Agency (EPA) defines nanotechnology as “the creation and use of structures, devices, and systems that have novel properties and functions because of their small size.”

1nm is one-billionth of a meter.  To put this in context, 1nm is one seven-thousandth of the width of a red blood cell or one eighty-thousandth of the width of a human hair. These are unimaginably small materials that are engineered to operate at the molecular and atomic level.

What’s more, there are now more than 1000+ consumer products on the market that utilize nanotechnology from the titanium particles in sunscreens to the silver contained in advanced first aid strips/plasters.  Nanotechnology will impact more than $2.5 trillion of manufactured goods by 2015.

Lux Research predicts that by 2014, 16% of manufactured goods in healthcare and life sciences will include nanomaterials.

To date, the United States leads the way in the fast evolving field of nanotechnology.  Between 2001 and 2010, the U.S. Government invested $12.4 billion in nanoscale science, engineering and technology through the U.S. National Nanotechnology Initiative (NNI).

The National Cancer Institute’s “NCI Alliance for Nanotechnology in Cancer” has an excellent website that outlines the potential impact of nanotechnology.

Some of the promising new cancer diagnostics and therapies based on nanotechnology include:

  • Positron Emission Tomography (PET) imaging agents that can be used to assess the responsiveness of tumors to chemotherapy
  • Chemically engineered adenovirus nanoparticle that stimulates the immune system. This is in phase 1 trials for chronic lymphocytic leukemia (CLL).
  • Cyclodextrin-based nanoparticle that encapsulates a small-interfering RNA (siRNA) agent that shuts down a key enzyme in cancer cells
  • CRLX101, a cyclodextrin-based polymer conjugated to camptothecin is in clinical trials with solid tumor patients
  • A nanoparticle based magnetic resonance imaging (MRI) contrast agent that binds to αvβ3-intregrin, a protein found on newly developed blood vessels associated with tumor development. This is in early clinical trials
  • Technology for the detection of cancer biomarkers such as prostate specific antigen (PSA)
  • Use of carbon nanotubes to improve colorectal cancer imaging.

Emerging companies such as Bind Biosciences are focusing on targeting cancer, inflammatory, cardiovascular diseases and infectious diseases with therapeutic nanoparticles.  Their lead product BIND-014 is currently in phase 1 development.

Innovations in nanotechnology will continue to present new product opportunities for biotechnology, pharmaceutical, medical imaging and diagnostics companies, and should be on everyone’s radar.

 

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