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Volume 8
AAPSIntroductionsinthe PharmaceuticalSciences
SeriesEditor
Claudio Salomon
NationalUniversityofRosario,Rosario,Argentina
FoundingEditor
ChicagoC ollegeofPha rmacy,MidwesternUniversity,DownersGrove,IL, USA
The AAPSIntroductionsinthePharmaceuticalSciences book series is designed to support pharmaceutical scientists at the point of knowledge transition. Springer and the American Association of Pharmaceutical Scientists (AAPS) have partnered again to produce a second series that juxtaposes the AAPSAdvancesinthePharmaceutical Sciences series. Whether shifting between positions, business models, research project objectives, or at a crossroad in professional development, scientists need to retool to meet the needs of the new scientiic challenges ahead of them. These educational pivot points require the learner to develop new vocabulary in order to effectively communicate across disciplines, appreciate historical evolution within the knowledge area with the aim of appreciating the current limitations and potential for growth, learn new skills and evaluation metrics so that project planning and subsequent evolution are evidence-based, as well as to simply “dust the rust off” content learned in previous educational or employment settings, or utilized during
former scientiic explorations. The Introductions book series will meet these needs and serve as a quick and easy-to-digest resource for contemporary science.
Editors
Jenny Ka Wing Lam and Philip Chi Lip Kwok
RespiratoryDeliveryofBiologics, NucleicAcids,andVaccines
First Edition
Editors
Jenny Ka Wing Lam Department of Pharmaceutics UCL School of Pharmacy, University College London, Brunswick Square, London, UK
Philip Chi Lip Kwok Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
ISSN 2522-834X e-ISSN 2522-8358 AAPS Introductions in the Pharmaceutical Sciences ISBN 978-3-031-47566-5 e-ISBN 978-3-031-47567-2
https://doi.org/10.1007/978-3-031-47567-2
Jointly published with American Association of Pharmaceutical Scientists
© American Association of Pharmaceutical Scientists 2023
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speciically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microilms 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 speciic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
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The publishers, 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 publishers nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publishers remain neutral with regard to jurisdictional claims in published maps and institutional afiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
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Preface
Biologics have emerged as an increasingly important class of therapeutics. Owing to their high speciicity and ability to target speciic components of the immune system, biologics are particularly useful in the treatment of cancers and immune-mediated diseases. In 2022, biologics accounted for over 40% of approvals by the Centre for Drug Evaluation and Research (CDER) of the United States Food and Drug Administration, a record high percentage of biologics to date. Although not classiied as biologics, nucleic acids such as small interfering ribonucleic acid (siRNA) and messenger ribonucleic acid (mRNA) also gained much attention in recent years. Their capability to manipulate the expression of virtually any gene makes them remarkably powerful therapeutic modalities to exploit “undruggable targets” to treat a wide range of diseases. The COVID-19 pandemic that began in 2020 has accelerated the development of new vaccine platforms that prominently feature viral vectors and mRNA vaccines. The landscape of pharmaceutical development is rapidly evolving, so biologics are expected to overtake small molecules and dominate the market in the foreseeable future.
Despite many biologics and vaccines already approved for treating or preventing lung diseases such as lung cancer, asthma, and respiratory viral infections, nearly all of them are parenterally administered. In contrast, administration through inhalation can directly target therapeutics to the site of action in the airways to maximise eficacy. This non-invasive route overcomes many drawbacks associated with parenteral routes, such as the requirement of trained personnel for administration, sterile formulations, and the risks of needlestick injuries and blood-borne diseases. Intranasal and orally inhaled vaccines can trigger mucosal immune response, which is lacking in conventional injected vaccines, and provide better protection against respiratory infections. Moreover, the high vascularisation of the lungs and nasal cavity can serve as an entry portal for the systemic delivery of small proteins and peptides. The potential of biologics, nucleic acids, and vaccines could be expanded to beneit more patients by developing formulations beyond parenteral
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administration, as the orally inhaled and nasal routes are already well­established for small drug molecules against respiratory diseases.
This book consists of nine chapters which give a comprehensive overview of the challenges and strategies in delivering a wide range of biologics and macromolecules to the respiratory tract, including antibodies, proteins, peptides, nucleic acids, and vaccines. It also covers the respiratory delivery of probiotics and bacteriophages, which have not yet been extensively studied but have shown promising potentials in improving health and ighting against infections. The pharmacokinetics of inhaled biological macromolecules, which is a poorly understood topic, are also discussed. We hope this book provides invaluable insights for readers who are working towards the goal of developing orally inhaled and nasal biologics, nucleic acids, and vaccines.
JennyKaWingLam PhilipChiLipKwok
BrunswickSquare,London,UK
Camperdown,NSW,Australia
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Con tents
DesignStrategiesof DryPowdersforPulmonaryDeliveryof PharmaceuticalPeptides
Hideyuki Sato
PulmonaryDeliveryofAntibodyfortheTreatmentofRespiratory Diseases
Thomas Secher and Nathalie Heuze-Vourc’h
DryPowderFormulationofMonoclonalAntibodiesforPulmonary Delivery
Kimberly B. Shepard, David Zeigler, W. Brett Caldwell and
Matthew Ferguson
AntimicrobialPeptidesandProteinsforInhalation
Yuncheng Wang, Rachel Y. K. Chang, Warwick J. Britton and Hak-
Kim Chan
PulmonaryDeliveryofNucleicAcids
Gemma Conte, Ivana d’Angelo, Joschka Mu ller, Benjamin Winkeljann,
Simone Carneiro, Olivia M. Merkel and Francesca Ungaro
IntranasalandInhaledVaccines
Michael Yee-Tak Chow and Jenny Ka Wing Lam
RespiratoryDeliveryofProbioticstoImproveLungHealth
Alex Seungyeon Byun, Luis Vitetta, Hak-Kim Chan and
Philip Chi Lip Kwok
RespiratoryDeliveryofBacteriophagesfortheTreatmentofLung Infections
Alex Seungyeon Byun, Hak-Kim Chan and Philip Chi Lip Kwok
PharmacokineticsofInhaledMedications–WhatDoWeKnow AboutBiologicalMacromolecules?
Audrey Huili Lim, Jinxin Zhao, Nusaibah Abdul Rahim, Jing Zhao,
Haiting Liu, Xiaoyan Yang and Yu-Wei Lin
Index
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AbouttheEditors
JennyKaWingLam
is an Associate Professor of Pharmaceutics at the UCL School of Pharmacy, University College London. Dr Lam obtained her MPharm and PhD from The University of Nottingham, UK. In her PhD study, she investigated the use of non-viral vectors for gene delivery. Dr Lam was then awarded the Maplethorpe Fellowship and continued her research in nucleic acid delivery in the Department of Pharmacy at King’s College London. She then joined the Department of Pharmacology and Pharmacy in the University of Hong Kong as Assistant Professor, and returned to the UK in 2022. Dr Lam’s research is focused on the development of novel delivery system for a wide range of therapeutics including small molecules, nucleic acids, and biologics, with special interest in the use of particle engineering methods to produce aerosol formulations for the treatment/prevention of respiratory diseases. She is the Principal Investigator of a number of competitive grants. She has published over 90 peer-reviewed articles and iled a number of patent applications on pulmonary drug delivery systems. In 2020, she was awarded the DDL (Drug Delivery to the Lung) Emerging Scientist Award which recognised her signiicant accomplishment and innovation in inhalation science.
PhilipChiLipKwok
is a Senior Lecturer in Pharmaceutical Sciences at the School of Pharmacy, The University of Sydney. He obtained his Bachelor of Pharmacy degree with First Class Honours in 2002 from this Faculty. He became a registered pharmacist after one year of training in a community pharmacy. Dr Kwok then undertook his PhD studies on pharmaceutical aerosol electrostatics in the Faculty of Pharmacy at The University of Sydney and graduated in 2007. He was a Research Associate in the same group until August 2011 and became an Assistant Professor in the Department of Pharmacology and Pharmacy at The University of Hong Kong in September 2011. Dr Kwok returned to The University of Sydney as a Lecturer in Pharmaceutical Sciences at
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