Microspheres based on synthetic polymers such as poly(methyl methacrylate) (PMMA) and PMMA blends are known for their medical and optical applications. The development of methods for processing polymeric microspheres using a nontoxic solvent, like supercritical carbon dioxide (SCCO2), is desirable. This work investigates the solubility and behavior of polymers (PMMA and PMMA/polycaprolactone blend) and solutes (cholesterol and albumin) in SCCO2 and SCCO2 + cosolvent (acetone, ethanol, and methylene chloride). The knowledge of solubility behavior of materials in SCCO2 aids in the selection and/or design of the most appropriate technique for materials processing. Processing PMMA-based polymers with pure SCCO2 leads to polymer swelling. The lack of polymer solubility in pure CO2 precludes their micronization by the RESS (rapid expansion of supercritical solutions) process, but on the other hand allows their impregnation. Polymer plasticization caused by CO2 can be exploited in the PGSS (particles from gas-saturated solutions) process. Addition of a liquid cosolvent to CO, enhances the dissolution of solutes and polymers. Precipitation of the studied polymers by antisolvent techniques seems feasible only by use of CO2 + methylene chloride. (C) 2003 Wiley Periodicals, Inc.