C Schugens

Polylactide macroporous biodegradable implants for cell transplantation. II. Preparation of polylactide foams by liquid-liquid phase separation

Potential of thermally induced phase separation as a porogen technique has been studied in an effort to produce a surgical implant suitable for cell transplantation. Emphasis has been placed on the liquid-liquid phase separation of solutions of amorphous poly DL-lactide and semicrystalline poly L-lactide in an 87/13 dioxane/water mixture. The related temperature/composition phase diagrams have been set up by turbidimetry, and the possible occurrence of a gel has been discussed. Freeze-drying of some phase-separated polylactide solutions can produce flexible and tough foams with an isotropic morphology. Interconnected pores of 1-10 microns in diameter are expected to result from the spinodal decomposition of the polylactide solutions with formation of co-continuous phases. Thermodynamics of the polymer/solvent pair has a decisive effect on the final macroporous foams, as shown by the dependence of their porosity, density, porous morphology, and mechanical behavior on molecular weight and crystallinity of polylactide and concentration of the original solutions. On the basis of the foam characteristics, potential of the liquid-liquid phase separation (spinodal decomposition) has been compared with the solid/liquid phase separation (solvent crystallization) as a porogen technique.

Polylactide Microparticles Prepared by Double Emulsion/Evaporation Technique. I. Effect of Primary Emulsion Stability

The process of microencapsulation of proteins by double emulsion/evaporation in a matrix of polylactide (PLA) can be divided into three successive steps: first, an aqueous solution of the active compound is emulsified into an organic solution of the hydrophobic coating polymer; second, this primary water-in-oil emulsion (w/o) is dispersed in water with formation of a double water-oil-water emulsion (w/o/w); third, the organic solvent is removed with formation of solid microparticles. This paper focuses on the effect of primary emulsion stability on the morphology and properties of polylactide microparticles loaded with bovine serum albumin (BSA) used as model drug. Depending on the stability of the primary emulsion, the internal structure of microparticles can be changed from a multivesicular to a matrix-like structure. Similarly, the average porosity can be controlled in a range from a few tenths of a micron to ca. 20 to 30 microns. This morphology control could find potential applications not only for the controlled drug delivery but also for the production of microporous particles intended for some specific applications, such as cell culture supports and chromatographic matrices. Although, the interplay of several processing parameters (polymer precipitation rate, polymer coprecipitation with interfacial compounds such as protein or surfactant, stirring rate, . . .) may not be disregarded, this study also indicated that a high loading of a hydrophilic drug can only be expected from a stable primary emulsion. When the stability of the primary emulsion is such as to prevent formation of macropores (>10 µm), the total pore volume is close to that of the originally dispersed aqueous drug solution.