Nanoparticles used for cancer drug delivery are made of micelles formed by blocky copolymers in aqueous solutions. Examples of technical challenges are how to maximize the drug concentration in the micelle core and how to recover dry micelles efficiently for storage and shipping. In a conventional 'freeze-dry' process, for example, the whole solution is frozen to preserve the micelle structure and to remove water by sublimation under vacuum. This project is motivated by an alternative approach where, instead of water, the solvent is a compressed fluid of variable polarity used near, either below or above, its critical temperature. Such a near critical fluid is expected to result in a better control of the drug transport and partitioning, and a more effective micelle separation via crystallization from the high-pressure micellar solution, without having to freeze the solvent. However, in order to explore and evaluate this concept, micellization and crystallization data are needed for a model diblock copolymer in near critical solvents. Toward this end, the project is proposed aimed at taking experimental phase behavior and separation data for compressible solutions of poly(ethylene glycol), PEG, poly(e- caprolactone), PCL, and their diblock, PEG-b-PCL, in subcritical and supercritical fluids, such as chlorodifluoromethane. The micellar order-disorder (ODT) transitions of block copolymers in such compressible solutions can be induced not only by increasing temperature, which leads to critical micelle temperature (CMT), but also by increasing pressure, which leads to critical micelle pressure (CMP). The micelles formed below CMT and CMP can be separated from solution by crystallization and solvent evaporation. The major experimental task is to characterize the cloud-point separation, crystallization, melting, and micellization of PEG-b-PCL in supercritical fluid solvents using high-pressure dynamic light scattering. Another experimental task is to precipitate the micelles by high-pressure crystallization upon cooling and to characterize their morphology through Tunneling Electron Microscopy (TEM), and their properties in water compared with those prepared in water and freeze-dried. Samples for the project will be custom synthesized and characterized in a separate larger project aimed at rapid-release nanoparticles for ovarian cancer drug delivery. Initial samples, lab space and equipment are available for this work in the Soft Materials Laboratory (SML).
Broader Impact The research will enable exploring a new micelle separation technology for producing nanoparticles needed for cancer drug delivery. This project will also help educate two doctoral students (one expected to graduate in 2008) and train two undergraduate students in characterizing self assembling molecules that lead to nanostructured materials.
