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IjeomaF.Uchegbu·
AndreasG.Schätzlein· AikateriniLalatsa·
DoloresRemediosSerranoLopezEditors
Fundamentals
ofPharmaceutical
Nanoscience
SecondEdition

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, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
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The publisher, the authors and the editors are safe to assume that the advice and information in this
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the editors give a warranty, expressed or implied, with respect to the material contained herein or for any
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The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
If disposing of this product, please recycle the paper.

Contents
https://t.me/med1917
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
https://t.me/med1917
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
https://t.me/med1917
Ijeoma F. Uchegbu, FMedSci, is UCL’s 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 ScientificOfficer 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 UK’s 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 first to show
that peptides could be delivered across the blood-brain barrier to elicit a pharmacological response, when presented as peptide drug nanofibers, and the first to demonstrate, via defin itive pharmacology and pharmacokinetics evidence, peptide
transport into the brain, using peptide nanoparticles delivered via the nose to brain
route. These findings led to the development of the enkephalin pain medicine
candidate Envelta
studies, Envelta
potential to cause significant constipation. Envelta has been out licensed for clinical
development.
The technology underpinning Envelta
Chemistry’s 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
Government’s 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 first prize in the Royal Society of
vii

viii About the Editors
https://t.me/med1917
Uchegbu’s scientific research work has been funded continuously for over two
decades by the UK’s Engineering and Physical Sciences Research Council and she
serves on the Biotechnology and Biological Sciences Research Council’s 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 first 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 scientific awards such as the Cantabria Labs Innovation Award in

About the Editors ix
https://t.me/med1917
Dermatology in 2022, the Roche Institute Award in Digital Health in 2020 and the
Research Pharmacy Award “Mario Martin Velamazan” in 2018. She has created one
of the first 3D printing laboratories at the School of Pharmacy in Complutense
University. Her research team has also a consolidated background in 3D printing
of microfluidic chips, especially for the manufacturing of nanomedicines, such as
liposomes and nanoparticles.

Chapter 1
https://t.me/med1917
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 benefit 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 molecule’s biological destination when administered for the treatment of disease, e.g. Doxil—liposomal doxorubicin (Gabizon
2001), Abraxane—albumin stabilised crystalline paclitaxel (Cortes and Saura 2010),
both cancer nanomedicines, and Onpattro—lipid siRNA nanoparticles (the world’s
first 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 scientific phenomenon—selfassembly. 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-assembly—controlled precipitation—in 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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