title: Protein entrapment in PEGylated lipid nanoparticles.
abstract: Defining appropriate delivery strategies of therapeutic proteins, based on lipid nanoparticulate carriers, requires knowledge of the nanoscale organization that determines the loading and release properties of the nanostructured particles. Nanoencapsulation of three cationic proteins (human brain-derived neurotrophic factor (BDNF), α-chymotrypsinogen A, and histone H3) was investigated using anionic nanoparticle (NP) carriers. PEGylated lipid NPs were prepared from self-assembled liquid crystalline phases involving monoolein and eicosapentaenoic acid. Inclusion of the antioxidant α-tocopherol favoured the preparation of stealth hexosome carriers. The purpose of the present work is to reveal the structural features of the protein-loaded lipid nanocarriers by means of high resolution small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). The obtained results indicate that protein entrapment is concentration-dependent and may significantly modify the inner liquid crystalline structure of the lipid nanocarriers through changes in the interfacial curvature and hydration.
authors.affiliation: CNRS UMR8612, Institut Galien Paris-Sud, 5 rue J.B. Clément, F-92296 Châtenay-Malabry Cedex, France. Angelina.Angelova@u-psud.fr
authors.forename: Angelina
authors.initials: A
authors.lastname: Angelova
authors.forename: Borislav
authors.initials: B
authors.lastname: Angelov
authors.forename: Markus
authors.initials: M
authors.lastname: Drechsler
authors.forename: Vasil M
authors.initials: VM
authors.lastname: Garamus
authors.forename: Sylviane
authors.initials: S
authors.lastname: Lesieur
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry*; D002919:Chymotrypsinogen / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; D008055:Lipids; D011092:Polyethylene Glycols; C579455:BDNF protein, human; D002919:Chymotrypsinogen
keywords: BDNF; Hexosomes; Neurotrophin; PEGylated liquid crystalline nanocarriers; Protein nanoencapsulation