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IjeomaF.Uchegbu· AndreasG.Schätzlein· AikateriniLalatsa· DoloresRemediosSerranoLopezEditors
Fundamentals ofPharmaceutical Nanoscience
SecondEdition
Fundamentals of Pharmaceutical Nanoscience
Ijeoma F. Uchegbu.Andreas G. Schätzlein Aikaterini Lalatsa Dolores Remedios Serrano Lopez
Editors
Fundamentals of Pharmaceutical Nanoscience
Second Edition
Editors
Ijeoma F. Uchegbu UCL School of Pharmacy University College London London, UK
Andreas G. Schätzlein UCL School
of Pharmacy University College London London, UK
Aikaterini Lalatsa CRUK Formulation Unit, Institute of Pharmacy and Biomedical Sciences University of Strathclyde
Dolores Remedios Serrano Lopez Departmento de Farmacia Galenica y TA Complutense University of Madrid Madrid, Madrid, Spain
Glasgow, UK Biomaterials, Bioengineering and Nanomedi
Institute of Pharmacy and Biomedical Scien
cine (BioN)
ces
Lab
University of Strathclyde Glasgow, UK
ISBN 978-3-031-59477-9 ISBN 978-3-031-59478-6 (eBook)
https://doi.org/10.1007/978-3-031-59478-6
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2013, 2024 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registe red company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
If disposing of this product, please recycle the paper.
Contents
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1 Introduction ... .. .. .. .. .. ... .. .. .. .. .. .. ... .. .. .. .. .. . 1
Ijeoma F. Uchegbu
Part I Nanomaterials Fabrication, Characterisation, and Use
2 Low-Molecular Weight Amphiphiles ... .. ... .. ... ... .. ... .. . 9
Marie-Christine Jones
3 Niosomes . .... .... ... .... .... ... .... .... ... .... ... .... 29
Maria Gioia Fabiano, Jacopo Forte, Patrizia Nadia Hanieh, Federica Rinaldi, Carlotta Marianecci, and Maria Carafa
4 Solid Drug Nanoparticles . .. .. ... .. .. ... .. .. ... .. ... .. .. . 63
Catherine Unsworth, Alison C. Savage, and Steve P. Rannard
5 Lipid Nanocapsules: Latest Advances and Applications .... .... . 89
Juan Aparicio-Blanco and Ana Isabel Torres-Suárez
6 Polymer-Drug Conjugates .. .. .. ... .. .. ... .. .. ... .. .. .. ... 109
Cristina Fante, María J. Vicent, and Francesca Greco
7 Polymeric Nanoparticles ... .. ... .. ... .. ... .. ... .. ... .. ... 139
Ijeoma F. Uchegbu
8 Porous Si-Based Nanosystems for Immunotherapy
Applications .... .... .... .... .... .... .... .... ..... .... . 165
Jiachen Li, Gabriela Corrêa Carvalho, Marlus Chorilli, and Hélder A. Santos
9 Ultrasmall-in-Nano .. .... .... .... .... .... ... .... .... .... 183
Ryan D. Mellor
v
Part II Concepts Underpinning the Application of Biomedical
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Nanomaterials
10 Transmucosal Drug Delivery: Main Physiological Features
and Modern Approaches ... .... ... .... .... .... ... .... .... 213
Shiva Vanukuru, Hisham Al-Obaidi, and Vitaliy V. Khutoryanskiy
11 Nanomedicines for Delivery Across the Blood–Brain
Barrier ... ... .. ... ... .. ... ... .. ... ... .. ... ... .. ... ... 241
Aikaterini Lalatsa, Debanjan Das, and Karim Osouli-Bostanabad
12 Non-deformable Nanoparticles and Transdermal
Penetration .............. ............... .............. 295
Majella E. Lane and Annisa Rahma
13 Nanotechnology and Hydrophobic Drug Solubilisation ........ .. 313
Lewis Dymock and Clare Hoskins
14 Active Targeting of Nanomedicines .............. ........... 337
Dolores Remedios Serrano Lopez, Aytug Kara, Bianca I. Ramirez, Irving O. Ramirez, Baris Őngoren, and Aikaterini Lalatsa
Part III Pharmaceutical Nanoscience Applications
15 Stimulus-Responsive Nanoparticles for Drug Delivery . .. ... .. . . 389
Nikolitsa Nomikou, Hamzah Masood, and Shiv Patel
16 Nanoparticles and Cancer Chemotherapy .......... .......... 423
Guojun Xiong and Ijeoma F. Uchegbu
17 Anti-infective Drug Nanosystems ........... ............. ... 451
Claire Ginn, Matthew J. Burton, and Abeer H. A. Mohamed-Ahmed
18 Use of Nanotechnology in the Formulation
of Vaccines .. .. .. .. ... .. .. .. .. .. ... .. .. .. .. .. .. ... .. .. 485
Yvonne Perrie and Cameron Webb
19 Peptides, Proteins and Antibodies .. .. ... ... .. ... .. ... ... .. . 511
Santina Iellamo De Gennaro and Aikaterini Lalatsa
20 Nanosystems and Medical Imaging .. .. ... .. ... .. ... .. ... .. . 655
Dong Luo, Shengxiang Fu, Li Liu, and Hua Ai
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
About the Editors
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Ijeoma F. Uchegbu, FMedSci, is UCLs Professor of Pharmaceutical Nanoscience, a fellow of the Academy of Medical Sciences, an honorary fellow of the Royal Society of Chemistry, a governor on the Wellcome board (one of the largest biomedical sciences research charities in the world), a member of the Academy of Medical Sciences Council and Chief ScienticOfficer of Nanomerics Ltd. In October 2024, Uchegbu will take up the position of President of Wolfson College at the University of Cambridge having been elected to the position in 2023. Uchegbu has served as Chair of the Academy of Pharmaceutical Sciences and chaired the UKs Engineering and Physical Sciences Research Council and Science Foundation Ireland grant prioritisation panels.
Uchegbu has studied the mechanisms of drug transport across biological barriers and created transformational drug transport nanoparticles. She was the rst to show that peptides could be delivered across the blood-brain barrier to elicit a pharmaco­logical response, when presented as peptide drug nanobers, and the rst to dem­onstrate, via den itive pharmacology and pharmacokinetics evidence, peptide transport into the brain, using peptide nanoparticles delivered via the nose to brain route. These ndings led to the development of the enkephalin pain medicine candidate Envelta studies, Envelta potential to cause signicant constipation. Envelta has been out licensed for clinical development.
The technology underpinning Envelta Chemistrys Emerging Technologies competition in 2017 and the Academy of Pharmaceutical Sciences Science Innovation Award in 2016. Three other medicine candidates based on this nanotechnology have further been out-licensed to pharma­ceutical companies.
Uchegbu has also won numerous prizes for her work and these include: the UK Governments Women of Outstanding Achievement in Science, Engineering and Tech­nology 2007, Royal Pharmaceutical Society Pharmaceutical Scientist of the Year 2012, Special Recognition Business of Science Leadership Award 2023 and others.
, which was designed to address the opioid crisis. In preclinical
showed no analgesic tolerance, reward-seeking behaviour or
won rst prize in the Royal Society of
vii
viii About the Editors
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Uchegbus scientic research work has been funded continuously for over two decades by the UKs Engineering and Physical Sciences Research Council and she serves on the Biotechnology and Biological Sciences Research Councils governing body.
Andreas G. Schätzlein has a track record of medicines development and transla­tional research in industry and academia. His research interests focus on the discov­ery and preclinical/clinical development of targeted anti-cancer drugs and nanomedicines and the understanding of their underlying biology. Andreas is a veterinary surgeon by training and, after completion of his doctorate on transdermal nanomedicines delivery, he joined the biotech start-up IDEA in Munich to develop this technology commercially.
In 1996, he joined academia at the Cancer Research UK Beatson Laboratories at the University of Glasgow where he became leader of the Experimental Therapeutics and Gene Medicines Group. There he was also responsible for setting up a unit that carried out analysis of pharmacokinetics and pharmacodynamics readouts from early phase translational oncology/nanomedicines trials using a good clinical laboratory practice framework. He is currently Professor of Translational Therapeutics at the UCL School of Pharmacy and co-founder and CEO of Nanomerics Ltd.
Aikaterini Lalatsa is a Reader in Nanomedicines and the Deputy Director of Cancer Research UK (CRUK) Formulation Unit (an MHRA-licensed manufacturing unit for sterile and oral new Investigational Medicinal Products for Phase I/II clinical trials) at the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), Univer­sity of Strathclyde. Aikaterini has a track record in development and translation of biologics, chemotherapeutics and nanomedicines working closely with industry towards translation into rst in human studies. She leads the Bio-engineering, Bio­materials and Nanomedicine (BioN) laboratory (originally at the University of Portsmouth and now at Strathclyde) that attracted funding from national and inter­national governments, charities and industrial sources. She is the inventor of four international patents, and her work has led to a paradigm shift in the non-invasive delivery of peptides, proteins and antibodies and chemotherapeutics across the blood-brain barrier. Aikaterini leads the MSc in Pharmaceutical Quality and Good Manufacturing Practise course at the University of Strathclyde.
Dolores Remedios Serrano Lopez received a European PhD with CUM LAUDE in
2013. After completing her doctorate studies, she worked as a Postdoctoral Fellow at the School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin (Ireland) as part of SSPC consortium (Synthesis and Solid State Pharmaceutical Center). She was appointed as a Lecturer in the Complutense University of Madrid in October 2015, and recently was promoted to Professor in 2023. She is the co-inventor of three patents and coauthor in over 80 publications. She received several scientic awards such as the Cantabria Labs Innovation Award in
About the Editors ix
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Dermatology in 2022, the Roche Institute Award in Digital Health in 2020 and the Research Pharmacy Award Mario Martin Velamazanin 2018. She has created one of the rst 3D printing laboratories at the School of Pharmacy in Complutense University. Her research team has also a consolidated background in 3D printing of microuidic chips, especially for the manufacturing of nanomedicines, such as liposomes and nanoparticles.
Chapter 1
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Introduction
Ijeoma F. Uchegbu
1.1 Pharmaceutical Nanoscience
Pharmaceutical nanoscience has progressed quite remarkably since the last edition of this volume. While it is still the case that most medicines are prepared as tablets, capsules and injectable solutions, it is now acknowledged that pharmaceutical nanoparticles are able to deliver real benet in the clinic (Fig. 1.1), with a number of new approved nanomedicines emerging. Of particular note are the advances in the fabrication of lipid nanoparticles.
These nanoparticles were pivotal to the develo pment of some of the Covid-19 vaccines (Thomas et al. 2021 )
Nanomedicines consist of functional nanoparticles presented in a liquid or solid matrix. Nanomedicines have been launched in which nanoscale properties have ensured unprecedented control of the molecules biological destination when admin­istered for the treatment of disease, e.g. Doxilliposomal doxorubicin (Gabizon
2001), Abraxanealbumin stabilised crystalline paclitaxel (Cortes and Saura 2010),
both cancer nanomedicines, and Onpattrolipid siRNA nanoparticles (the worlds rst siRNA medicine), indicated for the treatment of Hereditary Transthyretin Amyloidosis (Urits et al. 2020). Additionally, nanoparticulate imaging agents have now been commercialised (Thakor et al. 2016), although a number of the iron oxide magnetic resonance imaging agents have since been withdrawn from commercial use. At the heart of these nanosystems lies a basic scientic phenomenonself­assembly. Most of the nanosystems discussed in this volume are the product of molecular design, which predisposes towards classical self-assembly or a form of self-assemblycontrolled precipitationin aqueous media. The resulting
I. F. Uchegbu (*) UCL School of Pharmacy, University College London, London, UK e-mail: ijeoma.uchegbu@ucl.ac.uk
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 I. F. Uchegbu et al. (eds.), Fundamentals of Pharmaceutical Nanoscience,
https://doi.org/10.1007/978-3-031-59478-6_1
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