NCTR-ORA Nanotechnology Core Facility
Office of Scientific Coordination
National Center for Toxicological Research (NCTR)
FDA Jefferson Laboratories Campus
Jefferson, Arkansas 72079
- 5 months at FDA (August 2014-present)
- Over 20 years experience in Nanotechnology with 10 years at the Frederick National Laboratory for Cancer Research on preclinical assessment of nanomedicines.
All aspects of nanotechnology regulatory research in medical products from synthesis of nanomaterial based drugs, imaging agents and devices, material characterization, in vitro biocompatibility and in vivo safety and efficacy assessment.
Proposed Research Project for FDA Fellow:
Nanoparticle-based therapeutic agents contain passivating surface coatings to minimize immune system recognition thereby prolonging their blood half-life and enhanced accumulation in tumor tissue by enhanced permeation and retention (EPR) effect. It is known that lack of this passivating coating will lead to immediate opsonization, macrophage uptake and liver and spleen distribution, minimizing the therapeutic efficacy of nanomedicines. The molecular weight, density, stability, hydrophobicity and uniformity of coatings dictate the product safety, biodistribution and efficacy. These critical attributes should be monitored for product quality and consistency to assure reproducible and predictable safety, biodistribution, and efficacy in clinical trials and beyond. Currently a limited number of tests are available to ascertain the quality of the product.
This research project is designed to address these limitations by developing novel methods to assess surface coatings with advanced instrumentation available at the NCTR-ORA Nanocore by:
- Synthesizing nanoparticles with variable degree of surface coatings similar to those used in nanomedicines in current products in clinical trials;
- Quantitative determination of the stability of coatings through developing orthogonal methods using HPLC-Charged Aerosol Detector (CAD), HPLC- Evaporative Light Scattering Detector (ELSD) Thermogravimetric Analysis (TGA), Quartz-crystal microbalance (QCM), separation through Field Flow Fractionation along with traditional techniques such as light scattering and electron microscopy for particle characterization;
- Conduct in vitro studies to elicit changes in protein binding and biocompatibility studies;
- Conduct in vivo pharmacokinetic studies of nanoparticles with variable degree of coatings to relate how coatings might effect safety and effectiveness;
- Develop standards for these test methods to assist in regulatory review of emerging technologies.
A Ph.D. degree in Chemistry, Material Sciences, Biomedical Engineering or Pharmaceutical sciences, preferably with background in nanomaterial synthesis, characterization and biological applications.
Selected Recent Publications:
Dobrovolskaia M.A.; Neun, B.W. Man, S.; Ye, X.; Hansen, M.; Patri, A.K.; Crist, R.M.; McNeil S.E., Protein corona composition does not accurately predict hematocompatibility of colloidal gold nanoparticles. Nanomedicine 2014, in press; doi: 10.1016/j.nano.2014.01.009
Iida, N.; Dzutsev, A.; Stewart, C.A.; Smith, L.; Bouladoux, N.; Weingarten, R.A.; Molina, D.A.; Salcedo, R.; Back, T.; Cramer, S.; Dai, R.M.; Kiu, H.; Cardone, M.; Naik, S.; Patri, A.K.; Wang, E.; Marincola, F.M.; Frank, K.M.; Belkaid, Y.; Trinchieri, G.; Goldszmid, R.S., Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science, 2013, 342(6161), 967-970.
Goldberg, M.S.; Hook, S.S.; Wang, A.Z.; Bulte, J.W.M.; Patri, A.K.; Uckun, F.M.; Cryns, V.L.; Hanes, J.; Akin, D.; Hall, J.B.; Gharkholo, N.; Mumper, R.J., Biotargeted nanomedicines for cancer: six tenets before you begin. Nanomedicine 2013, 8, (2), 299-308.
Crist, R.M.; Grossman, J.H.; Patri, A.K.; Stern, S.T.; Dobrovolskaia, M.A.; Adiseshaiah, P.P.; Clogston,J.D. McNeil, S.E., Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory. Integrative Biology 2013, 5 ,(1), 66-73.
Wei, A.; Mehtala, J.G.; Patri, A.K., Challenges and opportunities in the advancement of nanomedicines. Journal of Controlled Release, 2012, 164, (2), 236-246.