Selection of the solvent system for the preparation of poly(D,L-lactic-co-glycolic acid) microspheres containing tumor necrosis factor-alpha (TNF-α)

Dichloromethane (DCM) and acetonitrile (ACN) are the most commonly used solvents for polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA). In order to select a suitable solvent system for the preparation of PLGA microspheres containing tumor necrosis factor-alpha (TNF-alpha), the stability of TNF-alpha when mixed with DCM and ACN under various phase conditions was investigated. When the TNF-alpha solution was emulsified into DCM to form a W/O emulsion prior to solvent evaporation using the W/O/W technique, a significant loss in activity of TNF-alpha was found. When the TNF-alpha was dispersed as a dry powder in the DCM phase, the protein was inactivated due to immediate hydration under the conditions of the solid/O/W system. Since TNF-alpha also was inactivated in a buffered saline containing ACN, the stability of the protein in microspheres prepared from an anhydrous solvent system was studied using ACN as the polymer solvent. Multiphase microspheres prepared by an anhydrous multiple emulsion process had a significantly higher loading efficiency of intact TNF-alpha than conventional matrix-type microspheres prepared by an anhydrous method using TNF-alpha powder and ACN. (C) 1998 Elsevier Science B.V.