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RakeshKumarTekade· NarendraKumarJainEditors
PEGylated Nanocarriers in Medicine and Pharmacy
PEGylated Nanocarriers in Medicine and Pharmacy
Editors

PEGylated Nanocarriers in Medicine and Pharmacy

Editors
Rakesh Kumar Tekade National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Palaj, Opp. Air force station, Gandhinagar, Gujarat, India
Narendra Kumar Jain Department of Pharmaceutical Sciences Dr. Hari Singh Gour University Sagar, Madhya Pradesh, India
ISBN 978-981-97-7315-2 ISBN 978-981-97-7316-9 (eBook)
https://doi.org/10.1007/978-981-97-7316-9
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 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, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms 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c 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 afliations.
This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore
If disposing of this product, please recycle the paper.

Preface

The editors welcome the readers into the fascinating world of PEGylation through this unique book, which embarks on a voyage via an inclusive landscape of histori­cal perspectives, groundbreaking discoveries, and technologies in medicine and the healthcare sector. Notably, since the advent of this technology in 1970, it seemingly offers remarkable properties to therapeutic molecules such as proteins, peptides, drugs, drug carriers, etc., through the properties bestowed upon them. PEGylation technology undeniably emerged as the show’s topper; the rest is history. This book answers all basic concepts and scientic queries, beginning with fundamental to contemporary advancements in the eld.
With this book, readers will be able to understand how PEGylation technology can enhance safety as well as therapeutic potential of drugs. It will shed light on how this technology can transform difcult-to-deliver therapeutic moiety into an extraordinary one. PEGylation enhances the solubility of a drug and makes it more water-friendly. PEG layering grants immunity from biological degradation and low­ers immune recognition. It precisely extends the biological half-life of an agent within the body, as if it offers a VIP tag to it by allowing it to stay longer in the physiological compartment. It is projected that the readers will be exceptionally amazed by the versatility of PEGylation technology as they progress to read the book page-by-page. From solubilization, drug delivery, and targeting avenues to diagnosis and theragnosis, it has an impactful resonance and echoes across all the elds of healthcare and medicine. The editors of this book invite readers to embark on an exciting journey to explore the innite potential of PEGylation, a simple yet immensely versatile technology.
Ahmedabad, Gujarat, India RakeshKumarTekade Sagar, Madhya Pradesh, India NarendraKumarJain
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Contents

1 PEGylated Pharmaceutical Nanocarriers . . . . . . . . . . . . . . . . . . . . . . . 1
Prashant Pingale, Sakshi Wani, Sahebrao Boraste, and Amarjitsing Rajput
2 Methods and Protocols for the Synthesis of PEGylated
Pharmaceutical Nanocarriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Ala’ Adnan Ali, Rakesh Kumar Tekade, and Randa S. H. Mansour
3 Topographic Properties of PEGylated Nanocarriers . . . . . . . . . . . . . . . 69
Aprameya Ganesh Prasad, Shivam Otavi, Mahima Mishra, and Rakesh Kumar Tekade
4 PEGylated Nanocarriers for Drug Delivery Applications . . . . . . . . . . . 107
Salome A. Chime and Mumuni A. Momoh
5 PEGylated Nanocarriers for Solubilization . . . . . . . . . . . . . . . . . . . . . . 137
Randa S. H. Mansour, Rakesh Kumar Tekade, and Ala’ Adnan Ali
6 PEGylation as a Tool to Alter Immunological Properties of
Nanocarriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Akhilesh Tiwari, Sourajyoti Goswami, Megha Joshi, Sanyam Gandhi, Pranay Soni, Muktika Tekade, Shubham Ramdas Mule, and Rakesh Kumar Tekade
7 PEGylated Nanocarrier as a Promising Tool for Site-Specific
Delivery of Therapeutics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Sweta Acharya, Niyati Lad, Aniket Navale, Simranjit Kaur, Aprameya Ganesh Prasad, and Rakesh Kumar Tekade
8 PEGylated Nanocarriers for Gene Therapy . . . . . . . . . . . . . . . . . . . . . . 239
Lopamudra Mishra, Lakshmi Kumari, Yash Sharma, Kanak Chahar, Satyam Khare, Preeti Patel, Dilpreet Singh, and Balak Das Kurmi
9 PEGylated Nanocarrier System for Nucleic Acid Delivery . . . . . . . . . . 275
Akhilesh Tiwari, Sreeharsha Nagaraja, Rakesh Sahu, and Muktika Tekade
vii
viii
Contents
10 PEGylated Nanocarriers for Protein and Peptide Delivery . . . . . . . . . 295
Tejas Girish Agnihotri, Vasu Peddinti, Shyam Sudhakar Gomte, Biswajit Rout, and Aakanchha Jain
11 PEGylation of Therapeutic Proteins and Peptides . . . . . . . . . . . . . . . . 317
Natasha Akojwar, Ankit Mishra, Pranali Mishra, Muktika Tekade, Shubham Ramdas Mule, and Rakesh Kumar Tekade
12 PEGylated Nanocarriers for Diagnostic Applications . . . . . . . . . . . . . . 345
Naveen Gupta, Ankit Mishra, Pran Kishore Deb, and Muktika Tekade
13 Multifunctional PEGylated Nanoparticles in Theragnosis . . . . . . . . . . 367
Akhilesh Tiwari, Muktika Tekade, Shubham Ramdas Mule, Girish Meravanige Basavarajappa, and Rakesh Kumar Tekade
14 Reversible PEGylation of Nanocarriers . . . . . . . . . . . . . . . . . . . . . . . . . 385
Mahima Mishra, Sweety Shah, Gagandeep Kaur, Aniket Navale, Heet Jani, Vaishnavi Chinkure, and Rakesh Kumar Tekade
15 Stimuli-Responsive PEGylated Nanocarriers . . . . . . . . . . . . . . . . . . . . 423
Samah Hamed Almurisi, Prasanthi Sri Nagindera Rao, and Thiagarajan Madheswaran
16 Beyond PEGylation “PEGylation and its Alternatives” . . . . . . . . . . . . 455
Sehasree Mohanta, Anuja Muley, Mansi Upadhyay, Dwiptesha Dahake, Muktika Tekade, Aprameya Ganesh Prasad, and Rakesh Kumar Tekade
17 Current Clinical, Regulatory, and Patent Aspects of PEGylated
Nanoproducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Sombir Saharan, Sajidul Hoque, Piyush Neware, V. Ravichandiran, and Vinod Gaikwad
18 Therapeutic and Pharmaceutical Applications of PEGylated
Nano-Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
Raheleh Shakeri, Seyedeh Zohreh Mirjalili, Ceyda Oksel Karakus, and Maliheh Safavi

Editors and Contributors

About the Editors

Rakesh Kumar Tekade, currently working as an Associate Professor at NIPER-Ahmedabad, is an aca­demic researcher with more than 15years of teaching and research experience. Before joining NIPER­Ahmedabad, he served as a Faculty at the Indian Institute of Technology (IIT), Jammu and at International Medical University, Malaysia, Kuala Lumpur. His current research involves developing t­to-purpose, translational, and novel targeted specic nano-biomaterials for biomedical applications. He has co-authored more than 350 publications (>16500 cita­tions; h-index: 65). He has edited 10 reference books with Elsevier (as editor-in-chief), 05 invited editorial articles, and 11 patent applications to his credit. For the past four consecutive years, he has been listed as one of the top 2% of researchers in Pharmacy and Pharmacology by Stanford University, USA.He was a recipient of several acclaimed awards, including Commonwealth Fellowships (British Council; University of Central Lancashire, UK), National Doctoral Fellowship (AICTE-NDF), Irish Government Postdoctoral Award (IRISH-PDF), and CSIR Senior Research Fellowship (CSIR-SRF), India and Junior Research Fellowship, India (AICTE-JRF), Best Associate Professor Award 2023, etc. to name the few.
Dr. Tekade underwent two postdoctoral trainings from The University of Hawaii, USA, and The University of Texas Southwestern Medical Center, USA. So far, he has trained 05 postdocs in his lab, guided 16 Ph.D. (08 completed and 8in progress), and supervised 75 master’s and biomedical science disserta­tions. He served/serving as a Principal Investigator for
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Editors and Contributors
various extramurally funded projects (worth more than2Crore) funded by DST, ICMR, MOSTI, etc. He is a recipient of the Pharma Innova Award by Troika Pharmaceuticals Ltd. for Best Research Mentor and the Best Thesis Award. Dr. Tekade is a grant reviewer for the FONDECYT funds (Chile), the National Science Centre (Poland), the French National Research Agency (ANR) (France), the Khwarizmi International Award (KIA) (Iran), and a referee for more than 30 reputed international journals. Dr. Tekade is an editor-in-chief of a book series entitled Advances in Pharmaceutical Product Development and Research Series. https://
www.elsevier.com/catalog/pharma/pharmaceutical­science/drug- delivery/advances- in- pharmaceutical- product- development- and- research.
Narendra Kumar Jain is an internationally renowned academician and researcher and a senior pro­fessor in India who superannuated in June 2014 after rendering more than 40 years of dedicated and distin­guished service as a teacher and 25years as full profes­sor. Starting his academic career in 1973, he worked as Lecturer in Pharmacy, Holkar College, Indore; Reader in Pharmaceutical Technology; M.S. University, Baroda; Professor and Principal, College of Pharmacy, Nasik; Professor and Head, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar; Principal, College of Pharmacy, New Delhi; Visiting Professor, Dubai Pharmacy College, Dubai (UAE); and Head, Pharmacy Department, Delhi University. Subsequent to his superannuation, Prof. Jain rendered his services as Director, ISF College of Pharmacy, Moga, Punjab, India, and as Emeritus Fellow (U.G.C.) at Rajiv Gandhi Technological University, Bhopal, M.P., India.
Prof. Jain is the author of over two dozen celebrated books in pharmaceutical sciences including a series on controlled and novel drug delivery systems and has con­tributed over 60 chapters in national and international books. He has to his credit over 500 publications in reputed pharmaceutical journals and has supervised 55 Ph.D. and 142 M.Pharm. candidates. He has been a reviewer for several international and national research journals. Professor Jain has been the recipient of IDMA
Editors and Contributors
xi
Research Award in Industrial Pharmacy in 1990, 1997, and 2004; Motan Devi Dandiya Award for Best Publication in Pharmacy in 1999; M.L.Khorana Prize for Best Research Paper in Pharmaceutics and Biopharmaceutics published in IJPS in 2003; Prof. M.L. Khorana Memorial Prize for Best Paper in the eld of Pharmaceutics and Biopharmaceutics published in IJPS during the year 2006; “Teacher of the Year 2003” award from the Association of Pharmaceutical Teachers of India; “Dr. (Mrs.) Manjushree Pal Memorial Award of the Association of Pharmaceutical Teachers of India for Best Pharmaceutical Scientist” in 2008; Schroff Memorial National Award for his outstanding contributions as an author, academician, and scientist by the Indian Hospital Pharmacists’ Association in 2008; and Motan Devi Dandiya Biennial Prize in Pharmacy for Best Publication in 2010.

Contributors

Samah Hamed Almurisi Department of Pharmaceutical Technology, School of
Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
Sweta Acharya National Institute of Pharmaceutical Education and Research
(NIPER) Ahmedabad, An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Palaj, Opp. Air force station, Gandhinagar, Gujarat, India
Tejas Girish Agnihotri Department of Pharmaceutics, National Institute of
Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India
Natasha Akojwar Department of Pharmaceutics, University Department of
Pharmaceutical Sciences, Nagpur University Campus, Nagpur, MS, India
Ala’AdnanAli Faculty of Pharmacy, Philadelphia University, Amman, Jordan
GirishMeravanigeBasavarajappa Department of Biomedical Sciences, College
of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
Sahebrao Boraste Department of Pharmaceutics, GES’s Sir Dr. M. S. Gosavi
College of Pharmaceutical Education and Research, Nashik, Maharashtra, India
KanakChahar Department of Pharmaceutics, ISF College of Pharmacy, Moga,
Punjab, India