Table Of ContentDrug Delivery with
Targeted Nanoparticles
In Vitro and In Vivo Evaluation Methods
edited by
Yılmaz Çapan
Adem Sahin
Hayrettin Tonbul
Published by
Jenny Stanford Publishing Pte. Ltd.
Level 34, Centennial Tower
3 Temasek Avenue
Singapore 039190
Email: [email protected]
Web: www.jennystanford.com
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Drug Delivery with Targeted Nanoparticles: In Vitro and In Vivo
Evaluation Methods
Copyright © 2022 Jenny Stanford Publishing Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced
in any form or by any means, electronic or mechanical, including
photocopying, recording or any information storage and retrieval system
now known or to be invented, without written permission from the
publisher.
ISBN 978-981-4877-75-6 (Hardcover)
ISBN 978-1-003-16473-9 (eBook)
Contents
Preface
xxvii
1. Particle Size Determination of Targeted Nanoparticles 1
Elif Bahar Yurttas, Tugba Gulsun, and Selma Sahin
1.1 Introduction 1
1.2 Nanotechnology 2
1.3 Nanoparticles 3
1.4 Targeted Nanoparticles 6
1.5 Particle Size Distribution 7
1.6 Particle Size Determination Methods 10
1.6.1 Photon Correlation Spectroscopy/
Dynamic Light Scattering 13
1.6.2 Laser Light Diffraction 15
1.6.3 X-Ray Diffraction Peak Broadening
Analysis 17
1.6.4 Scanning Electron Microscopy 18
1.6.5 Transmission Electron Microscopy 19
1.6.6 Atomic Force Microscopy 20
1.6.7 Other Methods 21
2. 1Ze.7t a PCootenncltuiasli oDne termination of Targeted Nanoparticles 2229
Melike Demirbolat, Zelihagül Değim, and İsmail Tuncer Değim
2.1 What Is Zeta Potential? 29
2.2 Determination Methods 31
2.2.1 Measuring the ZP by Electrophoresis 31
2.2.2 Tunable Resistive Pulse Sensing 32
2.3 Characteristics of the ZP 32
2.3.1 pH 33
vi Contents
2.3.2 Ionic Strength 33
2.3.3 Size Effect 34
2.3.3.1 Present charge 34
2.3.3.2 Conductivity 35
2.3.3.3 Concentration 37
2.3.3.4 Dilution 39
2.3.3.5 Stability 40
2.3.3.6 Reproducibility 42
2.3.3.7 Population 42
2.3.3.8 Pores and surface coating 43
2.3.3.9 Size 44
2.3.3.10 Temperature 45
2.4 Golden Standards and General Protocol for ZP
Measurement 45
2.4.1 Reagents and Dispersants 45
2.4.2 Cleaning of the Zeta Cell or Cuvette 45
2.4.3 Equipment 46
2.4.4 Sample Preparation 46
2.4.5 Colored and Fluorescent Samples 47
2.4.6 Using Buffers with Metallic Ions 48
2.4.7 Measuring the ZP in a Cell Culture Medium 48
2.5 Effect of the ZP on Targeting 48
3. 2St.6a biliCtoy nocfl uTasirogne ted Nanoparticles 5507
Susan D’Souza
3.1 Introduction 57
3.2 Significance of Stability Assessment 59
3.3 Physical Stability 62
3.3.1 Particle Size and Size Distribution 62
3.3.2 Structure and Morphology 63
3.3.3 Surface Chemistry and Surface Charge 64
3.3.4 Particle Growth via Aggregation or
Agglomeration 65
Contents vii
3.3.5 Reconstitution Properties 66
3.4 Chemical Stability 66
3.4.1 Amount of Drug and Degradation 66
3.4.2 Drug Release 68
3.4.3 Drug Leakage 68
3.4.4 Light Stability 70
3.4.5 Biological Activity 70
4. 3Im.5p acCt oonfc PluEsGiyolnast ion on Targeted Nanoparticulate 72
Delivery 77
Yeşim Aktaş, Merve Çelik Tekeli, and Sedat Ünal
4.1 Introduction 77
4.2 Passive Targeting 79
4.3 Active Targeting 79
4.4 Brain Targeting 80
5. 4Li.g5a ndTsu amnodr R Teacregpettoinrsg for Targeted Delivery of 86
Nanoparticles: Recent Updates and Challenges 97
Ankit Javia, Denish Bardoliwala, Mital Patel, and
Ambikanandan Misra
5.1 Introduction 98
5.2 Approaches to Targeted Drug Delivery 100
5.2.1 Passive Targeting 101
5.2.2 Active Targeting 103
5.3 Receptors for Targeted Drug Delivery and
Challenges 105
5.3.1 Receptor-Specific Challenges 105
5.3.1.1 Identification of receptors 105
5.3.1.2 Expression characteristics of
receptors 108
5.3.1.3 Receptor accessibility 109
5.3.1.4 Cellular uptake of receptors 110
viii Contents
5.4 Ligand-Based Targeted Drug Delivery:
Opportunities and Challenges 111
5.4.1 Selection of Ligand 111
5.4.2 Ligand Size 114
5.4.3 Conjugation of a Targeting Ligand with
a Drug/Nanocarrier 115
in vivo
5.4.4 Ligand Immunogenicity 116
5.5 Types and Fate of Targeted Nanoparticles 116
6. 5C.h6a raFctuetruizraet Piornos opfe Bctios laongdic Caol nMcolulesicounle –Loaded 119
Nanostructures Using Circular Dichroism and Fourier
Transform Infrared Spectroscopy 131
Ayhan Parlar, Prabir Kumar Kulabhusan, Hasan Kurt,
Büşra Gürel, Milad Torabfam, Başak Özata, and Meral Yüce
6.1 Introduction 131
6.2 Circular Dichroism 133
6.2.1 Sample Preparation and Measurement 134
6.2.2 Drug-Loaded Nanoparticle
Characterization by CD 135
6.3 Fourier Transform Infrared Spectroscopy 137
6.3.1 Sample Preparation and Measurement 139
6.3.2 Application of FTIR Spectroscopy
for Drug-Loaded Nanoparticle
Characterization 140
7. 6Ev.4a luaCtoionnc loufs iSotnim uli-Sensitive Nanoparticles in vitro 114437
Naile Ozturk, Asli Kara, and Imran Vural
7.1 Introduction 147
7.2 Stimuli-Responsive Nanocarriers 149
7.3 Stimuli-Responsive Drug Release 152
7.3.1 Internal Stimuli 153
7.3.1.1 pH stimuli 153
Contents ix
7.3.1.2 Redox stimuli 156
7.3.1.3 Enzyme stimuli 158
7.3.2 External Stimuli 160
7.3.2.1 Light stimuli 161
7.3.2.2 Ultrasound stimuli 164
7.3.2.3 Thermal stimuli 167
7.3.2.4 Magnetic stimuli 171
7.3.3 Multistimulation 173
7.4 Evaluation of Stimuli Response in Cell Culture 175
7.4.1 Endolysosomal Escape 175
7.4.2 Cytotoxicity 179
8. 7A.n5a lytCiocanlc Tluescihonni ques for Characterization of 180
Nanodrugs 191
Asuman Doğanay, Nurdan Atιlgan, Bahar Koksel Ozgen, and
Pelin Gurbetoglu
8.1 Introduction 192
8.2 Analytical Characterization of Nanodrugs 193
8.2.1 Drug Encapsulation and Loading Capacity 194
8.2.1.1 Drug-loading content and
drug-loading efficiency 194
8.2.1.2 Drug entrapment/incorporation
efficiency 194
8.2.2 Techniques for Chemical Composition of
Nanodrugs 195
8.2.2.1 Chromatographic techniques 195
8.2.2.2 Spectroscopic techniques 197
8.2.2.3 Calorimetric techniques 198
8.2.3 Purification Techniques of Nanodrugs 199
8.2.3.1 Filtration 200
8.2.3.2 Centrifugation 200
8.2.3.3 Dialysis 200
x Contents
8.2.3.4 Diafiltration 201
8.2.3.5 Size-exclusion chromatography 201
8.2.3.6 Electrophoresis 201
8.3 Physicochemical Characterization of Nanodrugs 201
8.3.1 Size and Surface Morphology 202
8.3.1.1 Dynamic light scattering 203
8.3.1.2 Microscopic techniques 203
8.3.2 Surface Area 205
In vitro
8.3.3 Surface Charge 206
In vitro
8.4 Drug Release Test Methods for Nanodrugs 207
8.4.1 Drug Release 207
8.4.1.1 Sample and separate method 207
8.4.1.2 Continuous flow method 208
8.4.1.3 Dialysis membrane methods 209
8.4.1.4 Combination methods 210
8.5 Stability of Nanodrugs 210
8.5.1 Effect of Dosage Form on Stability 211
8.5.2 Stability Issues Affecting Nanomaterial
Properties 211
8.5.2.1 Changes to particle size and
size distribution 212
8.5.2.2 Changes to particle
morphology/shape 212
8.5.2.3 Self-association 212
8.5.2.4 Sedimentation/creaming 213
8.5.2.5 Changes in the surface charge 213
8.5.2.6 Change in the dissolution/release
rate of the active ingredient 214
8.5.2.7 Drug leakage from a
nanomaterial carrier 214
8.5.2.8 Changes in the chemical
composition 215
8.5.2.9 Interaction with the formulation
or container closure 215
