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Shedding the Hydrophilic Mantle of Polymersomes

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Shedding the Hydrophilic Mantle of Polymersomes PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/100612 Please be advised that this information was generated on 2021-10-03 and may be subject to change. Polymeric vesicles for drug delivery over the blood-brain barrier and in vivo Imaging René Pascal Brinkhuis Polymeric vesicles for drug delivery over the blood-brain barrier and in vivo imaging Een wetenschappelijke proeve op het gebied van de Natuurwetenschappen, Wiskunde en Informatica Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J. Kortmann, volgens besluit van het college van decanen in het openbaar te verdedigen op maandag 10 december 2012 om 13.30 uur precies door René Pascal Brinkhuis geboren op 11 april 1981 te Deventer Promotoren: Prof. dr. ir. J.C.M. van Hest Prof. dr. F.P.J.T. Rutjes Manusscriptcommissie: Prof. dr. R.J.M. Nolte Prof. dr. D. Hoekstra (UMC Groningen) Prof. dr. O.C. Boerman (UMC Nijmegen) Druk: Ipskamp drukkers B.V., Enschede ISBN: 978-90-9027254-2 Contents Contents ............................................................................................................................................................................. 3 Preface ............................................................................................................................................................................... 5 Polymeric Vesicles in Biomedical Applications .................................................................................................... 9 1.1 Introduction ............................................................................................................................... 10 1.2 Block Copolymers ...................................................................................................................... 14 1.2.1 Synthetic polymers ............................................................................................................. 15 1.2.2 Bio(hybrid) polymers ......................................................................................................... 16 1.2.3 Polymeric vesicles with non-bilayer structures .............................................................. 19 1.3 Structural Factors ...................................................................................................................... 20 1.3.1 Stealth-like behaviour ........................................................................................................ 20 1.3.2 Size ....................................................................................................................................... 21 1.3.3 Shape ................................................................................................................................... 24 1.4 Release and Permeabilisation Mechanisms ............................................................................ 25 1.4.1 Triggered Disruption .......................................................................................................... 26 1.4.2 Controlled Permeability ..................................................................................................... 28 1.5 Surface Functionality ................................................................................................................ 32 1.5.1 Surface topology ................................................................................................................. 32 1.5.2 Surface functionalization ................................................................................................... 34 1.6 Conclusion .................................................................................................................................. 38 1.7 References .................................................................................................................................. 38 Functionalized Polymersomes Based on Poly-butadiene-b-poly(ethylene glycol) ............................... 43 2.1 Introduction ............................................................................................................................... 44 2.2 Results and Discussion .............................................................................................................. 46 2.2.1 Block copolymer synthesis ................................................................................................ 46 2.2.2 Polymersome formation and functionalization ............................................................... 49 2.2.3 Surface functionalization and cell adhesion ..................................................................... 51 2.3 Conclusion .................................................................................................................................. 53 2.4 Acknowledgements ................................................................................................................... 53 2.5 Experimental Procedures ......................................................................................................... 54 2.6 References .................................................................................................................................. 58 Size Dependent Biodistribution and SPECT Imaging of 111In-labelled Polymersomes ......................... 61 3.1 Introduction ............................................................................................................................... 62 3.2 Results and Discussion .............................................................................................................. 64 3.3 Conclusion .................................................................................................................................. 70 3.4 Acknowledgment ....................................................................................................................... 71 3.5 Experimental Procedures ......................................................................................................... 71 3.6 Notes and References ................................................................................................................ 73 Peptide-Mediated Blood-Brain Barrier Transport of Polymersomes ........................................................ 75 3 4.1 Introduction ............................................................................................................................... 76 4.2 Results and Discussion .............................................................................................................. 77 4.3 Conclusion .................................................................................................................................. 83 4.4 Acknowledgement ..................................................................................................................... 84 4.5 Experimental procedures .......................................................................................................... 84 4.5.1 Synthesis and characterisation .......................................................................................... 84 4.5.2 Polymersome formation and peptide conjugation .............................................................. 86 4.5.3 Phage display for selection of GM1-binding peptides ...................................................... 88 4.5.4 In vitro evaluation ............................................................................................................... 89 4.5.5 In vivo evaluation ................................................................................................................ 91 4.6 References .................................................................................................................................. 92 Brain and Organ Distribution of G23, Scrambled G23 and RI7217 Tagged Polymersomes ................ 95 5.1 Introduction ............................................................................................................................... 96 5.2 Results and Discussion .............................................................................................................. 97 5.3 Conclusion and Perspective .................................................................................................... 101 5.4 Acknowledgement ................................................................................................................... 101 5.5 Experimental Procedures ........................................................................................................ 102 5.6 Notes and references ............................................................................................................. 103 Shedding the Hydrophilic Mantle of Polymersomes ...................................................................................... 105 6.1. Introduction ............................................................................................................................ 106 6.2. Results and Discussion ........................................................................................................... 108 6.3. Conclusion ............................................................................................................................... 112 6.4 Acknowledgement ..................................................................................................................
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