title: Focused Ultrasound as a Scalable and Contact-Free Method to Manufacture Protein-Loaded PLGA Nanoparticles.
abstract: OBJECTIVE
  Although nanomaterials are under investigation for a very broad range of medical applications, only a small fraction of these are already commercialized or in clinical development. A major challenge for the translation of nanomedicines into the clinic is the missing scalability of the available lab scale preparation methods and, ultimately, non-identical samples during early and late research.
  
  
  METHODS
  Protein-loaded PLGA nanoparticles using focused ultrasound in an emulsion solvent diffusion method were prepared in different batch sizes to evaluate achievable mean size, protein loading, and yield.
  
  
  RESULTS
  Using the same equipment, nanoparticles could be prepared in batch sizes from 1 mg to 2.5 g. Size and yield were directly controllable by the amount of incident energy with good reproducibility. The nanoparticles displayed similar mean size, protein loading, and nanoparticle yield in batch sizes over three orders of magnitude. A scalable purification method based on diafiltration was established.
  
  
  CONCLUSIONS
  The proposed method enables for feasibility studies during early research using just a small amount of polymer and protein, while at the same time it allows for larger scale production at later stages. As the proposed method further relies on contact-free energy transmission, it is especially suited for the preparation of clinical research samples.
authors.affiliation: Department of Pharmacy, Biopharmaceutics & Pharmaceutical Technology, Saarland University,, Campus, Building A4.1,, 66123, Saarbrücken, Germany, stefan.schiller@external.merckgroup.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schiller
authors.forename: Andrea
authors.initials: A
authors.lastname: Hanefeld
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014465:Ultrasonics / Q000379:methods
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D011506:Proteins; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
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