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Sachin Kumar Singh ·
Monica Gulati · Srinivas Mutalik ·
Muralikrishnan Dhanasekaran ·
Kamal Dua Editors
Polymeric
Micelles:
Principles,
Perspectives and
Practices
Polymeric Micelles: Principles, Perspectives
and Practices
Sachin Kumar Singh
•
Monica Gulati
•
Srinivas Mutalik
•
Muralikrishnan Dhanasekaran
•
Kamal Dua
Editors
Polymeric Micelles:
Principles, Perspectives
and Practices
Editors
Sachin Kumar Singh
School of Pharmaceutical Sciences
Lovely Professional University
Phagwara, Punjab, India
Monica Gulati
School of Pharmaceutical Sciences
Lovely Professional University
Jalandhar, Punjab, India
Srinivas Mutalik
Department of Pharmaceutics
Manipal College of Pharmaceutical
Science
Manipal, Karnataka, India
Muralikrishnan Dhanasekaran
Harrison
School
of Pharmacy
Auburn University
Auburn, AL, USA
Kamal Dua
Discipline o
f Pharmacy
University of Technology Sydney
Sydney, NSW, Australia
ISBN 978-981-99-0360-3 ISBN 978-981-99-0361-0 (eBook)
https://doi.org/10.1007/978-981-99-0361-0
# The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore
Pte Ltd. 2023
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
transmission or information stora
ge 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 specific 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 a
ssume 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 affiliations.
This Springer imprint is published by the register
ed company Springer Nature Singapore Pte Ltd.
The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721,
Singapore
Preface
Polymeric micelles (PMs) are supramolecular configurations formed by amphiphilic
block copolymers in aqueous medium. The amphiphilic block copolymers consist of
hydrophilic and hydrophobic segments that have self-assembly property and are able
to form various self-assembled structures including spherical, lamellar, and vesicles.
This depends on their critical packaging parameter and microphase separation
process. For the formation of PMs, the critical micelle concentration (CMC) of
block copolymers plays a very critical role. This not only ensures their self-assembly
but their thermodynamic stability in the solution as well. Above their CMC value,
the hydrophilic segment forms the "corona" while the hydrophobic segment forms
the "core" of the PMs. In addition, the flexible and functional chemistry of these
block copolymers offers the tailoring of physicochemical traits of the PMs for a
specific application. This property imparts ease of functionalization to PMs for their
utilization in biomedical applications.
In agreement with this, these smart nanocarriers have immense potential to
overcome the challenges associated with existing treatment strategies or conven-
tional formulations. This includes poor dissolution rate, lack of site specificity, poor
oral bioavailability, poor in vivo stability, and the associated adverse effects. Their
nano-size and ease of functionalization have made it possible to deliver therapeutic
drugs, nucleic acids, proteins, and phytoconstituents to localized diseased sites to
maximize their clinical benefits while limiting unwanted side effects. In addition,
PMs could be designed as diagnostic and theranostic nanocarriers to improve the
clinical diagnosis of diseases and offer simultaneous treatment monitoring.
This book thoroughly reviews the advancements made in the designing and
application of PMs for drug delivery, covering the synthesis of amphiphilic block
copolymers and their types, functional chemistry of copolymers required for
targeting and sensing, characterization and biomedical applications of PMs.
1. This book provides the possibilities required in the designing of PMs in a range of
different d rug delivery approaches to the researchers working on this area. This
would be the first book to address the molecular parameters of amphiphilic block
copolymers required in functionalizing PMs for drug delivery applications.
2. This book presents the recent advances in PMs such as co-delivery, sensing,
theranostics, delivery of nucleic acids, proteins, and many more.
v
vi Preface
3. This book attracts a range of audiences including clinical researchers working in
the field of drug delivery, diseases diagnosis, undergraduate and postgraduate
students from various disciplines such as pharmacy, immunology, pharmacology,
pharmacognosy, biotechnology, and health sciences.
Phagwara,
Punjab, India Sachin Kumar Singh
Jalandhar, Punjab, India Monica Gulati
Manipal, Karnataka, India Srinivas Mutalik
Auburn, AL, USA Muralikrishnan Dhanasekaran
Sydney, NSW, Australia Kamal Dua
7
Contents
1 Synthesis, Self-Assembly, and Functional Chemistry
of Amphiphilic Block Copolymers .......................... 1
Vimal Arora, Divya Dhawal Bhandari, Ritika Puri,
Naveen Khatri, and Harish Dureja
2 Advances in Polymer Optimization for Enhanced Drug
Delivery .............................................. 27
Mayank Kashyap, Deepanshi Pathak, Shivani Gupta, Aanawi Tiwari,
Mansi Sharma, Debdarshan Dutta, Radhika Sharma, Saritha Shetty,
and R. Rachana
3 Dynamics of Micelle Formation ............................ 53
Anupama Sikder, Saurabh Shah, Shashi Bala Singh,
and Saurabh Srivastava
4 Types of Polymeric Micelles for Controlled Drug Release ........ 69
Divya Mahajan, Divya Suares, R. Rachana, and Saritha Shetty
5 Drug Solubilization and Drug Release from Polymeric Micelles ... 8
Ganesh Vambhurkar, Naitik Jain, Dadi A. Srinivasarao,
Paras Famta, Shashi Bala Singh, and Saurabh Srivastava
6 Physical and Analytical Techniques Used for the
Characterization of Polymeric Micelles ...................... 111
Amulya Etikala, Shweta Nene, Shashi Bala Singh,
and Saurabh Srivastava
7 Stimuli-Sensitive Polymeric Micelles for Biomedical
Applications .......................................... 125
Kaushal K. Jain, Akanksha Yogesh Kadam, Yashika Tomar,
and Gautam Singhvi
viivii
viii Contents
8 Nucleic Acid-Based Micellar Therapy for the Treatment
of Different Diseases .................................... 155
Subhasri Bogadi, Divya Pamu, Lavanya Mude,
Madhukiran Parvathaneni, Pavan Kumar Chintamaneni,
and Veera Venkata Satyanarayana Reddy Karri
9 Polymeric Micelles in the Delivery of Therapeutic
Phytoconstituents ...................................... 175
Jayesh S. Unde and Rahul Shukla
10 Diagnostic Applications of Surface-Engineered Polymeric
Micelles .............................................. 203
Jaskiran Kaur, Monica Gulati, Kamal Dua, Leander Corrie,
Ankit Awasthi, and Sachin Kumar Singh
11 Ligand Conjugated Polymeric Micelles for Targeted
Delivery of Drug Payloads in Cancer Therapy ................ 211
Simran Deep Kaur, Sachin Kumar Singh, Dinesh Kumar Chellappan,
Alaa A. Al jabali, Kamal Dua, and Deepak N. Kapoor
12 Polymeric Micelles in the Delivery of Proteins ................. 231
Sumel Ashique, Ashish Garg, Afzal Hussain, Shvetank Bhatt,
Ankur Agrawal, and Neeraj Mishra
13 Regulatory Aspects for Polymeric Micelles ................... 253
Anshita Gupta Soni, Renjil Joshi, Deependra Soni, Ujala Gupta,
Mayur Aalhate, and Pankaj Kumar Singh
14 Toxicological and Regulatory Challenges in Design
and Development of Polymeric Micelles ..................... 267
Ankur Kaul, Bhavna Kumar, and Dimple Sethi Chopra
15 S
tabili
ty of Polyme ric Micelles and Their Regulatory Status ...... 277
Indhumathi
Thirugnanasambandham, Kalaiselvi Aasaithambi,
Imrankhan Nizam, and Gowthamarajan Kuppusamy
About the Editors
Editors and Contributors
Sachin Kumar Singh a Professor at School of Pharmaceutical Sciences, Lovely
Professional University, India, holds his Master of Pharmacy in Pharmaceutical
Analysis from J.S.S. College of Pharmacy, Ooty, Tamil Nadu, India, and holds a
Ph.D. degree in Pharmaceutical Sciences from Karpagam University, Coimbatore,
India. He has completed one DST-SERB-funded project on the development of
SNEDDS of Polypeptide-k for the treatment of diabetes mellitus. Dr. Singh has
published more than 200 research papers with cumulative impact of 400 and
coauthored 10 book chapters. He has two granted Indian patents and two granted
Australian patents. Dr. Singh has reviewed more than 75 research papers upon
invitation from publishers of high repute such as Elsevier, American Chemical
Society, Bentham Sciences, and Royal Pharmaceutical Society. He has graduated
8 Ph.D. students and 30 Master of Pharmacy students and currently graduating
3 master’s and 6 Ph.D. students. Currently, his h-index is 27 with total citations
>2300. In January 2020, he received Dr. B.C. Deb memorial award for populariza-
tion of science by Indian Science Congress Association at 107th Indian Science
Congress held at UAS Bengaluru. He is the first recipient from the field of Pharma-
ceutical Sciences to receive this award. He is also a recipient of 2014 Bharat Shiksha
Ratan Award given by Global Society for Health and Educational Growth, Delhi,
India. His core area is improving oral bioavailability of poorly water-soluble drugs
using various formulation approaches including nanotechnology, complexation,
solid dispersion, and liquisolid technology.
Monica Gulati is the Registrar and Executive Dean at the School of Pharmaceutical
Sciences, Lovely Professional University, India, with more than 25 years of teach-
ing, industry, research, and administrative experience. Having completed her
B. Pharm., M. Pharm., and Ph.D. from UIPS, Panjab University, Chandigarh,
Dr. Gulati served for two years in the R&D department of Panacea Biotec. Shifting
later on to academia, she has served for more than 18 years at LPU in various
academic and administrative roles. Her research forte is enhancing bio-performance
of drug molecules, phytochemicals and probiotics, metabiotics, and other
biotherapeutics using conventional and novel dosage forms especially in the area
ixix
of colon targeting. She holds a keen interest in the quality control parameters of
delivery systems. She has more than 150 high-impact publications and 15 invited
book chapters to her credit, with an H-index of 28 and RG score of 39.05. She has
been granted four Indian patents and three Australian patents. She is on the editorial
and review board of more than 25 journals.
x Editors and Contributors
Sriniv
as
Mutal
i
k works as Professor and Head of the Department of Pharmaceutics
in Manipal College of Pharmaceutical Sciences, Manipal. He has completed his Ph.
D. in 2004 from Manipal Academy of Higher Education and 3 years of postdoctoral
studies from the University of Queensland, Australia, and was a visiting researcher at
A-Star Institute, Singapore, in 2016. Dr. Mutalik has good professional experience
in academics and in the pharmaceutical industry at different capacities. Dr Mutalik
has published more than 175 papers in reputed journals and has 10 patents to his
credit. He has presented research findings at various national and international
conferences and delivered several guest lectures. Dr. Mutalik has received several
research grants from funding agencies such as DBT, DST, ICMR, AICTE, SERB,
BIRAC, VGST, BRNS, and several pharmaceutical companies. He has received
several awards like Dr. TMA Gold Medal Award for Outstanding Research, Best
Poster/Oral Presentation Awards, Distinguished Alumni Award, APTI Young Phar-
macy Teacher Award, VGST Award for Best Research Paper, etc. Dr. Mutalik is
supervisor for several Ph.D. and PG students. He is the Life Member of various
professional organizations. Dr. Mutalik’s research interests include development and
evaluation of novel drug delivery systems and nanopharmaceuticals.
Muralikrishnan
Dhanasekaran graduated B. Pharm. in 1992 from Annamalai
University and obtained M. Pharm. in 1995, and a PhD degree in 1999 from
Jadavpur University, India. He received Junior Research Fellowship (JRF) and
Senior Research Fellowship (SRF) of the Council of Scientific and Industrial
Research (CSIR), Ministry of Science and Technology, Govt. of India.
Dr. Dhanasekaran has nearly 30 years of research experience in various synthetic
drugs and botanicals i
ncluding Indian and Western medicinal plants. While in the
Harrison School of Pharmacy, he has worked as a principal investigator of several
research projects funded by the Alzheimer’s Association and pharmaceutical
companies. Furthermore, he received several school and university level awards
for devoted teaching in the field of Graduate and Pharm. D programs. He has edited
4 books, published 102 scientific research articles in peer-reviewed journals,
40 book chapt
ers, and 200 abstracts in national and international meetings. He has
guided 12 M.S. and Ph.D. students as a mentor and has served as a committee
member for more than 30 graduate students. For the last many years,
Dr. Dhanasekaran has been working as a reviewer in NIH, Alzheimer’s Association,
and for severa l SCI journals and grants.
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