Stimuli Responsive Drug Delivery Systems : From Introduction to Application

370 Pages·2010·9.17 MB·English

by  Bajpai

Stimuli Responsive Drug
Delivery Systems: From
Introduction to Application
Anil Bajpai
Sandeep Shukla
Rajesh Saini
Atul Tiwari
iSmithers – A Smithers Group Company
Shawbury, Shrewsbury, Shropshire, SY4 4NR, United Kingdom
Telephone: [phone] Fax: [phone]
http://www.ismithers.net
First Published in 2010 by
iSmithers
Shawbury, Shrewsbury, Shropshire, SY4 4NR, UK
©2010, Smithers Rapra
All rights reserved. Except as permitted under current legislation no part
of this publication may be photocopied, reproduced or distributed in any
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the prior permission from the copyright holder.
A catalogue record for this book is available from the British Library.
Every effort has been made to contact copyright holders of any material reproduced
within the text and the authors and publishers apologise if any have been overlooked.
Every effort has been made to contact copyright holders of any material
reproduced within the text and the authors and publishers apologise if
any have been overlooked.
ISBN: 978-1-84735-416-7 (hardback)
978-1-84735-417-4 (softback)
978-1-84735-418-1 (ebook)
Typeset by Argil Services
Printed and bound by Lightning Source Inc.
P
reface
With the advancement of unique and novel synthetic strategies in chemical sciences,
a great impetus has been gained by the pharmaceutical and biomedical fields, which
have become the most vital interdisciplinary areas of fundamental and applied
research devoted to elevating the lifespans of humans and animals. Apart from the
ethical viewpoint of humanities, pharmaceutical science has travelled a long path and
has emerged as the fastest growing and most capital enriched sector in the business
world. The recent past has witnessed a great change in the field of pharmaceutical and
biomedical research due to the evolution of numerous modern scientific areas such as
combinatorial chemistry, drug designing, genomics, proteomics and many more.
The concept of designing smart or responsive materials has emerged as a boost to drug
administration approaches and has led to the evolution of drug-targeting strategies to
treat complex diseases like cancer and deeply seated tumours. The way the particular
disease has to be treated depends on the responsiveness of the drug formulation, which
in turn is regulated by the chemical architecture of the drug carrier system. Thus,
now it is the sole responsibility of polymer chemists to fabricate well-characterised
novel stimuli responsive systems which could be effectively and comfortably utilised
to treat complex diseases with ever better performance. Obviously, this could be
feasible only when one has complete understanding of the underlying functioning of
the system and deeper insights into the basic polymer and pharmaceutical chemistry
involved. This book of eight chapters has been written owing to a fascination by the
challenges behind designing a suitable responsive drug-delivery system and imparting
necessary fundamental backgrounds of the drug-delivery problems.
Beginning with the introduction of controlled and responsive drug-delivery systems,
Chapter 1 also discusses mathematical models to describe the mechanistic features
of the drug-release process. In Chapter 2 a detailed account of pH-responsive drug-
delivery systems has been given, which includes various kinds of pH stimuli systems,
necessary theory, applications and a description of various drug-delivery systems.
Chapter 3 details the response of drug-delivery systems to the temperature of the
medium by giving various types of systems and associated phase transition behaviours.
Chapter 4 covers magnetic-field-induced drug-delivery systems and presents its various
aspects. The chapter also includes the underlying theory of magnetic drug targeting,
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Stimuli Responsive Drug Delivery Systems: From Introduction to Application
nanoparticles as drug carriers, chemical routes of incorporating iron oxide into the
polymer matrix and its applications.
Chapter 5 focuses on the responses of the drug-delivery systems to the applied external
electric field. The content of this chapter highlights the theory and models involved and
the application of electrically responsive drug-delivery systems. Chapter 6 pertains to
the swelling-controlled drug-delivery systems and involves various theoretical models
being employed in the drug-delivery process, types of swelling-controlled systems and
their applications. A description of how the drug-delivery process responds to the
presence of chemical agents has been provided in Chapter 7. Moreover, this chapter
discusses the role of molecularly imprinted gels, proteins, antigens, enzymes, thrombin,
glucose, lectins and so on in regulating the drug-delivery process.
Finally, in Chapter 8 we have reviewed the commercially available polymer-based
drug-delivery systems and technologies. Among several biodegradable polymers,
only a few of them have been accepted so far by the food and drug administration
as safe materials for human and animal consumption. Also, we have discussed the
mode of synthesis of chemical compounds that are currently available in the industry.
Valuable, deeply hidden information has been extracted from the patented literature.
Technical information about the state-of-the-art products being sold to consumers is
appended along with their modus operandi. This will help researchers to tailor their
research and development programs such that their materials could be accepted in
the market.
We hope that the book will not only cater to the needs of the researchers engaged in
designing controlled drug-delivery systems but will also provide an essential basis to
both undergraduate and postgraduate students of pharmacy and chemistry.
Prof. Anil K. Bajpai
Dr Sandeep Shukla
Dr Rajesh Saini
Dr Atul Tiwari
iv
C
ontents
1. Introduction .................................................................. 1
1.1 Introduction .......................................................................1
1.2 Responsive Stimuli-sensitive Materials ................................1
1.2.1 Swelling-controlled Systems ............................................4
1.2.2 Magnetic-sensitive Release Systems ................................4
1.3 Concept of Controlled Drug Delivery .................................5
1.3.1 Controlled Drug Delivery ...............................................8
1.3.2 Advantages of Controlled Drug Delivery ......................10
1.3.3 Types of Controlled Drug Delivery ...............................11
1.3.3.1 Diffusion-controlled System .........................11
1.3.3.1.1 Reservoir Devices .........................................14
1.3.3.1.2 Matrix Devices .............................................14
1.3.3.1.3 Laminated Matrix Devices ...........................16
1.3.3.2 Swelling-controlled Systems ..........................16
1.3.3.3 Chemically Controlled Systems ....................17
1.3.3.3.1 Matrix with Covalently Attached Drug ........17
1.3.3.3.2 Devices with Entrapped Drug .......................18
1.3.3.4 Other Delivery Systems ................................18
1.4 Targeted Drug Delivery .....................................................18
1.4.1 Major Schemes of Targeted Drug Delivery ...................19
1.4.2 Types of Targeting Methods .........................................20
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Stimuli Responsive Drug Delivery Systems: From Introduction to Application
1.4.2.1 Physical Targeting .........................................20
1.4.2.2 Passive Targeting ..........................................21
1.4.2.3 Active Targeting ...........................................21
1.5 Mathematical Modelling of Drug Delivery [80] ................22
1.5.1 Factors Operative in Release Mechanisms ....................24
1.5.2 Empirical and Semi-empirical Mathematical Models ....24
1.5.2.1 Peppas Equation ...........................................25
1.5.2.2 Hopfenberg Model .......................................25
1.5.2.3 Cooney Model ..............................................26
1.5.2.4 Artificial Neural Networks ...........................27
1.5.3 Mechanistic Realistic Models .......................................29
1.5.3.1 Theories Based on Fick’s Law of Diffusion ...29
1.5.3.2 Theories Considering Polymer Swelling ........36
1.5.3.3 Theories Considering Polymer Swelling and
Polymer and Drug Dissolution .....................40
1.5.3.4 Theories Considering Polymer Erosion/
Degradation .................................................45
1.6 Some Milestones in the Fields of Controlled Drug
Delivery ............................................................................51
1.7 Future Challenges and Scope ............................................53
2 pH-Sensitive Release Systems ...................................... 65
2.1 Introduction .....................................................................65
2.2 Swelling Behaviour of pH-sensitive Hydrogels in Buffer
Solution ............................................................................66
2.3 Phase Transition Behaviour of pH-responsive Hydrogels ..68
2.4 Types of pH-sensitive Hydrogels .......................................70
2.4.1 Ionic Hydrogels ............................................................70
2.4.1.1 Anionic Hydrogels ........................................70
2.4.1.2 Cationic Hydrogels .......................................71
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Contents
2.4.1.3 Polyamphoteric Hydrogels ...........................72
2.4.2 Non-ionic Hydrogels ....................................................73
2.5 Properties of pH-sensitive Hydrogels ................................74
2.6 Drug Release Mechanisms from Hydrogel Devices ...........74
2.7 Applications of pH-sensitive Hydrogels ............................75
2.7.1 Poly(ε-caprolactone) (PCL) ...........................................83
2.7.2 Poly(ethylene glycol) (PEG) ..........................................83
2.7.3 Chitosan .......................................................................84
2.7.4 Alginate ........................................................................86
2.7.5 Poly(2-acrylamido-2-methylpropane sulfonic acid
(AMPS) sodium salt) ....................................................89
2.8 pH-sensitive Hydrogel in Insulin Delivery .........................90
2.9 pH-sensitive Copolymers and their Application to Nasal
Delivery ............................................................................93
2.10 pH-dependent Systems for Glucose-stimulated Drug
Delivery ............................................................................93
2.11 Application of pH-sensitive Polymers to Colon-specific
Drug Delivery ...................................................................95
3 Temperature-sensitive Release Systems ...................... 107
3.1 Introduction ...................................................................107
3.2 Types of Temperature-sensitive Hydrogels ......................110
3.2.1 Negative Temperature-sensitive Hydrogels .................110
3.2.2 Positive Temperature-sensitive Hydrogels ...................111
3.2.3 Thermoreversible Gels ................................................111
3.3 Thermosensitivity ...........................................................111
3.4 Phase Transition with LCST and UCST ..........................113
3.5 Factors Affecting LCST ..................................................114
3.6 Phase Transition Behaviour of Stimuli-responsive
Hydrogels .......................................................................114
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Stimuli Responsive Drug Delivery Systems: From Introduction to Application
3.7 Important Preparation Methods of Temperature-sensitive
Hydrogels .......................................................................118
3.7.1 Emulsion Polymerisation ............................................118
3.7.2 Frontal Polymerisation Synthesis of Temperature-
sensitive Hydrogels .....................................................119
3.7.3 A Little Introduction of Atom Transfer Radical
Polymerisations (ATRP) Techniques ...........................121
3.8 Delivery of Biologically Active Agents by LCST
Hydrogels .......................................................................123
3.9 Applications of Temperature-sensitive Hydrogels in
Drug Release ..................................................................126
3.10 Uses of Thermoreversible Hydrogels ...............................133
4 Magnetically Responsive Targeted Drug Delivery ..... 143
4.1 Introduction ...................................................................143
4.2 Concept of Magnetic Drug Targeting ..............................144
4.3 Nanoparticulates in Magnetic Targeted Drug Delivery ...151
4.4 Theory: Magnetic Basics .................................................153
4.5 Types of Magnetism ........................................................155
4.5.1 Paramagnetism ...........................................................155
4.5.2 Ferromagnetism and Ferrimagnetism ..........................156
4.5.3 Antiferromagnetism ....................................................159
4.6 Magnetic Field ................................................................160
4.7 Magnetic Material ..........................................................160
4.8 Incorporation of Iron Oxide ...........................................163
4.9 Methods of Incorporation of Iron Oxide ........................163
4.9.1 Coprecipitation ..........................................................163
4.9.2 Thermal Decomposition .............................................164
4.9.3 Microemulsions ..........................................................164
4.9.4 Miscellaneous .............................................................165
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Contents
4.10 Advantages of Magnetic-controlled and Targeted Drug
Delivery ..........................................................................165
4.11 Applications of Magnetic-controlled and Targeted
Drug Delivery .................................................................167
4.11.1 Drug Delivery to Tumours ..........................................168
4.11.2 MRI Contrast Agents .................................................170
4.11.3 Hyperthermia .............................................................171
4.11.4 Cell Labelling and Magnetic Separation .....................172
4.12 Future Challenges and Prospects .....................................173
5 Electric Sensitive Release Systems .............................. 185
5.1 Introduction ...................................................................185
5.2 Theories of Electrosensitive Release System ....................186
5.2.1 Donnan Equilibrium Theory ......................................186
5.2.2 Mixture Theory ..........................................................190
5.2.3 The Generalised Triphasic Theory ..............................190
5.2.4 Refined Multieffect-coupling Electric-Stimulus
(rMECe) Model ..........................................................192
5.2.4.1 Theory and Formulation ............................192
5.2.4.2 Boundary and Initial Conditions ................195
5.2.4.3 Discretisation of the Transient Governing
Equations of the MECe Model ...................198
5.3 Measurement of Bending Angle ......................................199
5.4 Application of Electrosensitive Release System ...............201
6 Swelling-controlled Release Systems .......................... 213
6.1 Introduction ...................................................................213
6.2 Swelling Studies ..............................................................215
6.2.1 Swelling Experiments .................................................215
6.2.2 Dynamics of Water Sorption .......................................216
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