title: A toolbox for the upscaling of ethanolic human serum albumin (HSA) desolvation.
abstract: Nanoparticles consisting of human serum albumin (HSA) play an emerging role in the development of new drug delivery systems. Many of these protein-based colloidal carriers are prepared by the well-known desolvation technique, which has shown to be a robust and reproducible method for the laboratory-scale production of HSA nanoparticles. The aim of the present study was to upscale the ethanolic desolvation process utilizing the paddle stirring systems Nanopaddle I and II in combination with a HPLC pump in order to find the optimal conditions for the controlled desolvation of up to 2000 mg of the protein. For characterization of the HSA nanoparticles particle size, zeta potential as a function of the pH, polydispersity index and particle content were investigated. The particle content was determined by microgravimetry and by a turbidimetry to allow optimized in-process control for the novel desolvation technique. Furthermore the sedimentation coefficient was measured by analytical ultracentrifugation (AUC) to gain deeper insight into the size distribution of the nanoparticles. The formed nanocarriers were freeze dryed to achieve a solid preparation for long-term storage and further processing. Particles ranging in size between 251.2 ± 27.0 and 234.1 ± 1.5 nm and with a polydispersity index below 0.2 were achieved.
authors.affiliation: Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. wacker@em.uni-frankfurt.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Wacker
authors.forename: Anja
authors.initials: A
authors.lastname: Zensi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kufleitner
authors.forename: Aaron
authors.initials: A
authors.lastname: Ruff
authors.forename: Jessica
authors.initials: J
authors.lastname: Schütz
authors.forename: Tobias
authors.initials: T
authors.lastname: Stockburger
authors.forename: Thomas
authors.initials: T
authors.lastname: Marstaller
authors.forename: Vitali
authors.initials: V
authors.lastname: Vogel
mesh_terms: D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D055808:Drug Discovery; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D006801:Humans; D008970:Molecular Weight; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*; D010316:Particle Size; D012709:Serum Albumin / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D005079:Excipients; D012709:Serum Albumin; D000431:Ethanol