| Micelles made of amphiphilic block copolymers can encapsulate hydrophobic drugs, not only to increase their effective solubility in blood and hence therapeutic efficacy, but also to alleviate chemotherapy side effects. Conventionally, such drug-containing micelles are prepared using incompressible liquid solvents that do not allow for a precise control over the micellization and drug encapsulation sequence. A better alternative is to use compressible near-critical fluid solvents that not only allow for such a control but also easily release the solid nanoparticles by decompression. This work demonstrates the benefits of mixed near-critical solvents. For example, a mixture of high-capacity dimethyl ether and high-selectivity trifluoromethane is found to be the best solvent for processing nanoparticles made of poly(ethylene glycol)-block-poly(a-caprolactone). This work also demonstrates that the solution history can affect the solid precipitate structure. For instance, the micellar structure initially found in solution can be rearranged upon collection if the polymer crystallizes at high pressures. If, however, one first reduces the pressure at elevated temperatures, and then crystallizes the polymer, the micellar structure can be preserved. This work also provides an overview of nanoparticles used for cancer drug delivery and explores new diblock, triblock and lipid materials that can improve either the drug loading or release or both. |
