Poly(ethylene carbonate) microspheres: manufacturing process and internal structure characterization

The granulocyte-macrophage colony stimulating factor (GM-CSF), a water-solu ble cytokine, was encapsulated in poly(ethylene carbonate) microspheres (MS ) by a double emulsion w(1)/o/w(2) solvent evaporation method. Poly(ethylen e carbonate) is a new polymer of high molecular weight (MW) and forms polym er matrices that are exclusively surface bioerodible. In the frame of this study, the influence of the polymer molecular weight and the polymer concen tration in the organic phase on the physico-chemical characteristics of the microspheres were investigated. Ninety percent of the microspheres had a d iameter ranging between 4 and 136 mu m, with a mean value of 30 mu m. The e ncapsulation ratios ranged from 2.22 to 2.51% (w/w) depending on the molecu lar weight of the polymer corresponding to an encapsulation efficiency of 7 0 to 100%, respectively. Independent of the polymer molecular weight used, the in vitro drug release was very low, ranging from 5.61 to less than 1% o f the total encapsulated GM-CSF amount. Scanning electron microscopy (SEM) analysis showed microparticles with spherical shapes and smooth surfaces co ntaining a few small globules. The inner structure of the microspheres appe ared to consist of a polymeric matrix surrounding numerous globules. These globules have different sizes, shape and distribution in the polymeric matr ix, depending on the concentration of the polymer solution and on the polym er molecular weight. In addition, it was demonstrated that the GM-CSF lower ed the interfacial tension between the GM-CSF aqueous solution and the meth ylene chloride organic phase. The active critical concentration was as low as 0.008 mg/ml. It was therefore suggested that this particular behavior co ntributed to the stabilization of the primary emulsion during the formation of the microspheres, leading to rather high encapsulation efficiency. (C) 2000 Elsevier Science B.V. All rights reserved.