(17c) Drug Delivery and Imaging Using Nanoparticles Produced by Block-Copolymer Directed Flash Nanoprecipitation

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.