title: Ion milling coupled field emission scanning electron microscopy reveals current misunderstanding of morphology of polymeric nanoparticles.
abstract: Nanoparticles (NPs) are currently used as drug delivery systems for numerous therapeutic macromolecules, e.g. proteins or DNA. Based on the preparation by double emulsion solvent evaporation a sponge-like structure was postulated entrapping hydrophilic drugs inside an internal aqueous phase. However, a direct proof of this hypothesized structure is still missing today. NPs were prepared from different polymers using a double-emulsion method and characterized for their physicochemical properties. Combining ion milling with field emission scanning electron microscopy allowed to cross section single NP and to visualize their internal morphology. The imaging procedure permitted cross-sectioning of NPs and visualization of the internal structure as well as localizing drugs associated with NPs. It was observed that none of the model actives was encapsulated inside the polymeric matrix when particle diameters were below around 470 nm but predominantly adsorbed to the particle surface. Even at larger diameters only a minority of particles of a diameter below 1 μm contained an internal phase. The properties of such drug loaded NPs, i.e. drug release or the observations in cellular uptake or even drug targeting needs to be interpreted carefully since in most cases NP surface properties are potentially dominated by the 'encapsulated' drug characteristics.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Donny
authors.initials: D
authors.lastname: Francis
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Samiha
authors.initials: S
authors.lastname: Mouftah
authors.affiliation: Nanotechnology Equipment Department, Hitachi High-Technologies Europe GmbH, Krefeld, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Steffen
authors.affiliation: Laboratory of Pharmaceutical Engineering (EA4267), University of Franche-Comté, Besançon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Beduneau
authors.affiliation: Laboratory of Pharmaceutical Engineering (EA4267), University of Franche-Comté, Besançon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Pellequer
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; Laboratory of Pharmaceutical Engineering (EA4267), University of Franche-Comté, Besançon, France. Electronic address: alf.lamprecht@uni-bonn.de.
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004655:Emulsions; D011108:Polymers
keywords: Double emulsion technique; Ion milling; Nanoparticle morphology; Nanoparticles; Polyester; Protein adsorption; Protein encapsulation