Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response

Context: The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. Objective: To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Methods: Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. Results: The spray dried particles were spherical, with a size range of about 2-3 mu m and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 degrees C (enthalpy: 170.61 J/g) and a degradation-onset of 180 degrees C for PEG 3350. PLGA 65:35 was amorphous, with a T-g of 43 degrees C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 degrees C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. Conclusion: This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 mu m) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.