Production of Protein-Loaded Polymeric Microcapsules by Compressed CO<INF>2</INF> in a Mixed Solvent

In view of developing new drug-delivery systems, microparticles of biocompatible polymer loaded with protein were produced using a supercritical antisolvent technique. As the polymer, poly(lactic acid) (PLA) of about 100 000 Da was used, whereas insulin was chosen as the protein model. To achieve microencapsulation, we started from a homogeneous solution of protein and polymer, to which the supercritical antisolvent is added; mixtures of dichloromethane and dimethyl sulfoxide were used to ensure the solubility of both the polymer and the protein. All experiments were performed in semicontinuous mode. A preliminary study with PLA alone was done in order to select the best operative condition and to control the particle dimension and their diameter distribution range, especially with mixtures of the two solvents. Then, the microspheres of PLA charged with insulin were produced; the average diameters ranged from 0.5 to 2 μm. The composition of these particles was determined analytically, and the protein bioactivity was checked.