Friday, October 13
8:30 Chairperson’s Remarks
Chairperson: Mansoor M. Amiji, R.Ph., Ph.D., Professor and Associate Department Chair, Department of Pharmaceutical Sciences and Co-Director, Nanomedicine Education and Research Consortium (NERC), Northeastern University
8:40 Multifunctional Polymeric Nanocarriers to Overcome Drug Resistance in Cancer
Mansoor M. Amiji, R.Ph., Ph.D.
The development of multidrug resistance (MDR) is a major cause of failure in chemotherapeutic management of cancer. Our strategy to overcome MDR in vivo relies on a multifunctional approach to optimize delivery of anticancer drugs to the tumor mass, increase the intracellular drug concentrations, and reverse of cellular resistance by modulating ceramide levels. The data show that tumor-targeted biodegradable polymer-based engineered nanocarriers (PENS) can co-encapsulate hydrophobic drugs, such as paclitaxel, with MDR modulators. These multifunctional PENS are able to deliver these agents inside the cell for maximum cytotoxicity in sensitive and resistant tumor cells. Long-circulating PENS show preferential tumor uptake by the enhanced permeability and retention effect in human tumor xenograft studies.
9:40 Nanoparticle Albumin Bound Technology
Michael Hawkins, M.D., Chief Medical Officer, American BioScience, Inc.
Nanoparticle Albumin Bound (nab?) technology binds albumin and hydrophobic molecules into nanoparticles without modifying either component and without the need for toxic solvents. Abraxane(?), a nab form of paclitaxel, is the first clinical application of this technology, permitting more rapid and higher bioavailability of paclitaxel compared to Cremophor-paclitaxel (Taxol?) formulations. Because albumin is not modified, Abraxane is also able to target tumors by exploiting endogenous albumin-mediated transport pathways to increase the delivery of paclitaxel to tumor cells. In clinical trials, Abraxane almost doubled the response rate of women with metastatic breast cancer compared to cremophor-paclitaxel.
10:10 Coffee Break, Poster & Exhibit Viewing
10:45 Polyketals: A New Biomaterial for Drug Delivery
Niren Murthy, Ph.D., Assistant Professor, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
In this presentation we will describe a new family of polymers developed in our laboratory termed the polyketals. The polyketals are polymers that have ketal linkages in their backbones. They hydrolyze via acid catalyzed hydrolysis into acetone and biocompatible diols. We have been able to formulate protein loaded microparticles with the polyketals, using a double emulsion procedure. We are currently investigating the ability of the polyketals to deliver therapeutic enzymes to macrophages for the treatment of acute liver failure.
11:15 Magnetic Nanoparticles for the Diagnosis and Treatment of Cancer
Dr. Stephen Barry, President, Preclinical Development, Alnis BioSciences, Inc.
Alnis BioSciences is making Magnagel nanoparticles that are comprised of magnetic cores, chemotherapeutic payloads, and tumor-homing ligands for the detection, diagnosis and treatment of cancer. Particles can be made to extremely well-defined diameters in the range of 20 nm, and each particle can be loaded with approximately 1000 chemotherapeutic molecules and targeted to tumor using 10s of ligands. The magnetic cores enable both MRI detection of particle location and particle heating, synergistically combining hyperthermic and chemotherapeutic functions within a single nanoparticle structure. These particles have demonstrated outstanding magnetic properties and distribution profiles in in vivo cancer models, and efficacy experiments have begun. The development of MagNaGel nanoparticles is supported by a contract with the National Cancer Institute.
|11:45 Panel Discussion with Speakers:
• What makes a good polymer?
• Is it a benefit for the polymer to be biodegradable?
12:15 Lunch on Your Own (Luncheon Workshop
1:30 Chairperson’s Remarks
Chairperson: Dr. Carol Dahl, Director for Global Health Technologies, Bill & Melinda Gates Foundation
1:40 Targeted Delivery to the Respiratory Tract of Nanoparticles and Microparticles of Vaccines, Anti-Virals, and Antibiotics for Developing Country Use
Robert E. Sievers, Ph.D., Professor, Department of Chemistry and Biochemistry, University of Colorado, Boulder, and Chief Executive Officer, Aktiv-Dry LLC
We have synthesized nanoparticles and microparticles of live attenuated measles virus vaccine at near-ambient temperatures ľ 50 šC without detectable loss of viral activity, when properly stabilized with sugar excipients and buffers. This was accomplished by Carbon Dioxide Assisted Nebulization with a Bubble Dryer (CAN-BD®). Aerodynamic particle diameters have ranged from 50 to 5000 nm for samples of measles vaccine, zanamivir, pyrazinamide, isoniazid, rifampin, capreomycin, amikacin, and moxifloxacin, which allows targeted delivery to the lungs and respiratory tract.
2:10 Nanoviricide against Influenza A
Anil R. Diwan, Ph.D., President, NanoViricides, Inc.
We are working on drug treatments based on our unique approach to nanomedicine. We call these drugs “nanoviricides™”. A nanoviricide is an agent that recognizes a specific virus particle, binds to it, neutralizes and then dismantles it. Nanoviricides are thus useful when vaccines fail or when a vaccine approach is not available or not suitable. In the case of influenza, available knowledge indicates that vaccines are several years behind the evolution of the field strain and therefore nanoviricides are probably going to be the only line of defense available. Recent developments indicating field drift and divergence in H5N1 strains have raised the specter that the vaccines currently in development or manufacture against H5N1 may have limited field success. Our strategy has been to develop a broad spectrum influenza nanoviricide (FluCide-I™), a group-specific nanoviricide (AviFluCide-HP™) against highly pathogenic avian influenza and a nanoviricide that is highly specific to H5N1 (AviFluCide-I). All three drugs are in preclinical stages. Both the results and implications of our in-vitro and in-vivo studies on these drugs will be discussed.
2:40 Polymer Nanospheres for Controlled Release of Viral Antigens
Dr. Trevor P. Castor, Cheif Executive Officer, Aphios Corporation
Aphios has developed an enhanced controlled release technology for nanoencapsulating potent viral antigens in biodegradable polymer nanospheres by utilizing SuperFluids, which are supercritical, critical or near-critical fluids with or without polar cosolvents (U.S. Patent, 2006). The use of SuperFluids reduces exposure of viral antigens such as HIV and Influenza to potentially denaturing organic solvents such as methylene chloride and ethyl acetate, and improves the stability of protein antigens in the body at ambient temperature for long periods, thereby enhancing the capability of nanoencapsulated vaccine antigens to induce the production of protective and neutralizing antibodies. This controlled release vaccine delivery technology has the capability to deliver different types and combinations of HIV or Influenza vaccine candidates including whole inactivated virus particles, DNA plasmids and/or subunit protein antigens. SuperFluids polymer nanoencapsulation technology will reduce cost by eliminating unnecessary processing steps while improving the manufacturing environment. Unlike currently available technologies, this technology is quite inexpensive, amenable to large-scale processing, and quite portable.
3:10 Close of Conference