Targeted liposomes for drug delivery across the blood - TI Pharma

185 Pages·2011·1.95 MB·English

Targeted liposomes for drug delivery
across the blood-brain barrier
ISBN: 978-90-39355220

© 2011 Inge van Rooy

Cover design: Mikenzo Communicatie, Utrecht, The Netherlands
Printed by: Ipskamp Drukkers B.V., Enschede, The Netherlands

Printing of this thesis was financially supported by:

Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands
J.E. Jurriaanse Stichting, Rotterdam, The Netherlands
Phospholipid Research Center, Heidelberg, Germany
BD Biosciences, Franklin Lakes, USA
Targeted liposomes for drug delivery
across the blood-brain barrier

Liposomen voor gericht geneesmiddeltransport
over de bloed-hersenbarrière
(met een samenvatting in het Nederlands)

PROEFSCHRIFT

ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge
het besluit van het college voor promoties in het openbaar te verdedigen
op maandag 18 april 2011 des middags te 2.30 uur

door

Inge van Rooy

geboren op 20 december 1982 te Waalre
Promotoren: Prof.dr.ir. W.E. Hennink
Prof.dr. G. Storm

Co-promotoren: Dr. E. Mastrobattista
Dr. R.M. Schiffelers
Beyond the line of blue -
The boundary of the star
Which turneth at the view
Of thy barrier and thy bar -
Of the barrier overgone
By the comets who were cast
From their pride, and from their throne
To be drudges till the last -
To be carriers of fire
(The red fire of their heart)
With speed that may not tire
And with pain that shall not part -

Edgar Allan Poe

Table of contents

Chapter 1 General introduction 9

Chapter 2 In vivo methods to study uptake of nanoparticles into the brain 27

Chapter 3 Comparison of five different targeting ligands to enhance 59
accumulation of liposomes into the brain

Chapter 4 Identification of peptide ligands for targeting to the 79
blood-brain barrier
Supplementary information to chapter 4 99

Chapter 5 Attaching the phage display-selected GLA peptide to 103
liposomes: factors influencing target binding
Supplementary information to chapter 5 121

Chapter 6 Preparation and characterization of liposomal formulations 123
of neurotensin-degrading enzyme inhibitors

Chapter 7 Summary and future perspectives 137

Appendices Nederlandse samenvatting 153
List of abbreviations 163
List of publications 167
Affiliations of collaborating authors 171
Curriculum vitae 175
Dankwoord 179

1
Chapter
General introduction