title: Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.
abstract: BACKGROUND
  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 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °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.
  
  
  CONCLUSIONS
  This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) 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.
authors.affiliation: a Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy , USciences , Philadelphia , PA , USA.
authors.forename: Curie
authors.initials: C
authors.lastname: Javiya
authors.affiliation: a Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy , USciences , Philadelphia , PA , USA.
authors.forename: Sriramakamal
authors.initials: S
authors.lastname: Jonnalagadda
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties / Q000187:drug effects; D013696:Temperature
chemical_list: D004337:Drug Carriers; D017382:Reactive Oxygen Species; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: Alveolar macrophages; NR8383; biodegradable; inflammatory response; parenteral; polymer blending; site-reaction