Levich Institute Seminar Announcement, 03/25/2008

Tuesday, 03/25/2008 2:00 PM Steinman Hall, Room #312 (Chemical Engineering Conference Room) Professor Robert Prud'homme Princeton University Chemical Engineering Department "Drug Delivery and Imaging Using Nanoparticles Produced by Block-copolymer Directed Flash NanoPrecipitation"

ABSTRACT

Nanoparticle formulations of hydrophobic drugs present unique opportunities for treatment of solid tumor cancers, for delivery of drugs by aerosol administration, and as a route to novel vaccine adjuvants. The common requirements of these applications are precise control of particle size and surface functionality. For cancer therapy particles in the size range of 100-200 nm passively pass through defects in the vasculature in tumors and deposit by "enhanced permeation retention". In addition to delivery, the ability to monitor the fate of the nanoparticles is also of important since anti-cancer agents are invariably toxic to healthy tissue. Our process --Flash NanoPrecipitation - a controlled precipitation process that produces stable nanoparticles at high concentrations using amphiphilic diblock copolymers to direct self-assembly enables the production of composite nanoparticles that enable simultaneous imaging and delivery. Uniform particles with tunable sizes from 50-500 nm can be prepared in an economical and scalable manner. The key to the process is the control of time scales for micromixing, polymer self-assembly, and particle nucleation and growth. The PEG protective layer creates long-circulating particles and the inclusion of PEG chains with terminal ligands allows drug targeting. The incorporation of gold nanoparticles, magnetic nanoparticles, or fluorophores into the composite particle enables imaging by x-ray, MRI, or confocal microscopy, respectively. The incorporation of up converting phosphor crystals into the composite nanoparticles enables a highly efficient form of photodynamic therapy.

BRIEF ACADEMIC/EMPLOYMENT BACKGROUND:

• 1969 BSE Chemical Engineering, Stanford University
• 1973 Graduate Studies Program in Environmental Science and Public Policy, Harvard University
• 1978 PhD Chemical Engineering, University of Wisconsin- Madison
• 1978-present Chemical Engineering, Princeton University (Professor: 1991)
• 1979 Research Engineer, E.I. DuPont and Co., Engineering Technology Laboratory, Wilmington, DE (June-Aug)
• 1984-1985 Research Engineer, AT&T Bell Laboratories, Plastics Research and Development Department, Murray Hill, NJ (sabbatical leave)
• 2001-2002 Chemistry Department, University of Sydney (sabbatical leave)

CURRENT RESEARCH INTERESTS:

Self-assembly and biomacromolecules. In the area of self-assembly, weak forces are used to control both the equilibrium phase behavior as well as the kinetics of assembly. Hydrophobically modified polymers interact with surfactant mesophases, lipid bilayer surfaces, colloids, or other amphiphilic polymers in aqeuous solution. Competitive kinetics of nanoparticle formation and block copolymer assembly can be tuned to create stable nano-particles for drug therapy. Self assembly in non-aqueous solutions can be driven by crystallization. The kinetics of self-assembly of block copolymers and wax crystals can be used to stabilize diesel fuels and crude oil against gelation. In these areas we use combinations of optical, rheological and scattering techniques to relate structure to properties. In the second area of biopolymers we work to understand how nature uses weak hydrogen bonding forces to tailor interactions between biomacromolecules. These forces determine polymer solubility and rheology. New techniques such as fluorescence probe photobleaching and osmotic stress diffraction allow us to probe molecular level interactions.

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