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Woodhead Publishing Series in Biomaterials
Biopolymer-Based
Composites
Drug Delivery and Biomedical
Applications
Edited by
Sougata Jana
Sabyasachi Maiti
Subrata Jana
Woodhead Publishing is an imprint of Elsevier
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List of contributors
Ayan K. Barui Department of Chemical Biology, CSIR-Indian Institute of Chemi-
cal Technology, Hyderabad, India; Academy of Scientific and Innovative Research
(AcSIR), Chennai, India
Vishnu S. Bollu Department of Chemical Biology, CSIR-Indian Institute of Chem-
ical Technology, Hyderabad, India; Academy of Scientific and Innovative Research
(AcSIR), Chennai, India
Diana M. Buitrago Universidad El Bosque, Bogotá, Colombia
Weiren Cheng Institute of Materials Research and Engineering, A*STAR, Singapore
Lucimara G. de La Torre State University of Campinas (UNICAMP), Campinas,
Brazil
Ismail Es¸ State University of Campinas (UNICAMP), Campinas, Brazil
Yenny M. García Universidad El Bosque, Bogotá, Colombia
José F. Ibla Universidad El Bosque, Bogotá, Colombia
Keerti Jain National Institute of Pharmaceutical Education and Research (NIPER),
Raebareli, India
Sougata Jana Gupta College of Technological Sciences, Asansol, India
Subrata Jana Indira Gandhi National Tribal University, Amarkantak, India
Ting Jiang Fudan University, Shanghai, China
Kai Jin Fudan University, Shanghai, China
Rajesh Kotcherlakota Department of Chemical Biology, CSIR-Indian Institute of
Chemical Technology, Hyderabad, India; Academy of Scientific and Innovative Research
(AcSIR), Chennai, India
Gloria I. Lafaurie Universidad El Bosque, Bogotá, Colombia
Xianpping Liu Fudan University, Shanghai, China
Ye Liu Institute of Materials Research and Engineering, A*STAR, Singapore
x List of contributors
Rahul Maheshwari BM College of Pharmaceutical Education and Research, Indore,
India
Sabyasachi Maiti Gupta College of Technological Sciences, Asansol, India
Nishi Mody Dr. H.S. Gour Vishwavidyalaya, Sagar, India
Sandra J. Morantes Universidad El Bosque, Bogotá, Colombia
Thays F. Naves State University of Campinas (UNICAMP), Campinas, Brazil
Susheel K. Nethi Department of Chemical Biology, CSIR-Indian Institute of Chem-
ical Technology, Hyderabad, India; Academy of Scientific and Innovative Research
(AcSIR), Chennai, India
Aline F. Oliveira State University of Campinas (UNICAMP), Campinas, Brazil
Zhiqing Pang Fudan University, Shanghai, China
Jenny E. Parraga Tampere University of Technology, Tampere, Finland
Chitta R. Patra Department of Chemical Biology, CSIR-Indian Institute of Chem-
ical Technology, Hyderabad, India; Academy of Scientific and Innovative Research
(AcSIR), Chennai, India
Amanda C.S.N. Pessoa State University of Campinas (UNICAMP), Campinas, Brazil
M. Prabaharan Hindustan Institute of Technology and Science, Chennai, India
Rajeev Sharma Dr. H.S. Gour Vishwavidyalaya, Sagar, India
Caroline C. Sipoli State University of Campinas (UNICAMP), Campinas, Brazil;
Federal University of Technology – Paraná (UTFPR), Apucarana, Brazil
P.R. Sivashankari Hindustan Institute of Technology and Science, Chennai, India
Muktika Tekade Technocrats Institute of Technology Campus, Bhopal, India
Rakesh K. Tekade National Institute of Pharmaceutical Education and Research
(NIPER) – Ahmedabad, Gandhinagar, India
Franciele F. Vit State University of Campinas (UNICAMP), Campinas, Brazil
Micaela T. Vitor State University of Campinas (UNICAMP), Campinas, Brazil
Suresh P. Vyas Dr. H.S. Gour Vishwavidyalaya, Sagar, India
Editors’ biographies
Prof. Sougata Jana is working at the Department of Pharmaceutics, Gupta College of
Technological Sciences, under Maulana Abul Kalam Azad University of Technology,
West Bengal, India. He is an MPharm (Pharmaceutics) from Biju Patnaik University of
Technology, Odisha, India. He is engaged in research for 10 years and in teaching for
9 years. He qualified the Graduate Aptitude Test in Engineering (GATE) examination in
the year 2005. He received “Gold Medal” from West Bengal University of Technology,
Kolkata, for standing first at the undergraduate level. The Indian Pharmaceutical
Association (IPA) Bengal branch, Kolkata, India, conferred on him the “M.N. Dev
Memorial Award” for securing the highest marks in the state of West Bengal in the
year 2005. He bagged the “Best Poster Presentation Award” at the 21st West Bengal
State Science and Technology Congress, 2014, Burdwan, and the “Outstanding Paper
Award” at the first Regional Science and Technology Congress, 2016, Bardhaman
Division, organized by the Department of Science and Technology (DST), Government
of West Bengal, and Bankura Christian College, West Bengal, India. He has published
30 research and review papers in different national and international peer-reviewed
journals. He has edited four books published by Elsevier, Springer, and Pharmamedix
India Publication Pvt. Ltd. More than 25 book chapters are also in his credit in Elsevier,
Wiley VCH, CRC Press, and Taylor and Francis group. He is a reviewer of various
international journals published by Elsevier, Wiley, Springer, Taylor and Francis, Dove
Press, etc. He is a life member of the Association of Pharmaceutical Teachers of India
(APTI) and Associateship (A.IC) from Institution of Chemists, India. He has success-
fully guided 16 postgraduate students for their research projects. He is working in the
field of drug delivery science and technology, including modification of synthetic and
natural biopolymers, microparticles, nanoparticles, semisolids, and interpenetrating
network system for controlled drug delivery.
xii Editors’ biographies
Dr. Sabyasachi Maiti is an MPharm, PhD, from Jadavpur University, Kolkata, India.
He is currently working as Professor at the Department of Pharmaceutics, Gupta
College of Technological Sciences, West Bengal, India. His research interest includes
modification of natural polysaccharides and design of novel drug delivery systems. He
has published more than 50 research and review papers in various international jour-
nals of repute. He has penned 20 book chapters for various international publishers
and edited two books for CRC Press and InTech. He is also working as coeditor for an
Elsevier book. He received research grants from national funding agencies such as All
India Council for Technical Education (AICTE), Science and Engineering Research
Board (SERB)-DST. He is associated with several professional bodies, such as IPA,
APTI, and Indian Science Congress Association (ISCA). He is a fellow of the Indian
Chemical Society and Institute of Chemists (India). He is a reviewer of Science Direct,
Bentham Science, Springer, Informa Healthcare, and other journals.
Prof. Subrata Jana obtained his PhD in organic chemistry from Indian Institute of
Engineering Science and Technology, Shibpur, India. His doctoral work was based on
the design and synthesis of abiotic receptors for the recognition of biologically active
neutral molecules and ions along with the development of synthetic methodologies.
He also studied the recognition process in the solution phase and in the solid state.
Overall, he has extensively studied the supramolecular behavior of the host–guest
Editors’ biographies xiii
interaction. Besides, he has worked on the development of synthetic methodologies
for substituted heterocyclics, such as pyrimidines, naphthyridines, quinolone, and
diazepines by exploiting the microwave protocol for green chemical synthesis. He
moved to University of Victoria, Canada, to work with Dr. Fraser Hof on supramo-
lecular and medicinal chemistry as a postdoctoral fellow, where he worked on the
synthesis of different receptors targeting N-methylated protein residue along with
anions. He then worked with Dr. Kenneth J Woycechowsky at University of Utah,
USA, on protein engineering and enzyme catalysis as a postdoctoral research asso-
ciate. He studied enzyme activity when the enzyme is encapsulated inside the cap-
sid, which is a nanocarrier and an excellent delivery vehicle for important biological
substrates, including drug molecules. Presently, he is working as Associate Professor
at Department of Chemistry, Indira Gandhi National Tribal University, Amarkantak,
Madhya Pradesh, India, and his current research focuses on the design and synthesis
of artificial receptors for the recognition of anions, cations, and N-methylated protein
residue. He is also working on biodegradable polymeric-based carrier systems for
the delivery of drug molecules by collaboration with pharmaceutical scientists. So
far he has published about 40 research papers in peer-reviewed international journals
and contributed more than 10 book chapters in different books published by inter-
nationally renowned publishers. He also serves as editorial board member for the
Journal of PharmaSciTech (ISSN: 2231-3788) and International Journal of Scientific
and Engineering Research (ISSN: 2229-5518), as well as reviewer for International
Journal of Biological Macromolecule (Elsevier) and Journal of PharmaSciTech and
Current Pharmaceutical Design (Bentham).
Biocomposites in therapeutic 1
application: current status and
future
Sabyasachi Maiti1, Sougata Jana1, Subrata Jana2
1Gupta College of Technological Sciences, Asansol, India; 2Indira Gandhi National Tribal
University, Amarkantak, India
1.1 Introduction
From the health care perspective, biomaterials can be defined as the materials that pos-
sess some novel properties that make them appropriate to come into immediate con-
tact with the living tissue without eliciting any adverse immune rejection reactions.
The biomaterials can be divided into the following categories: (1) synthetic (metals,
polymers, ceramics, and composites); (2) naturally derived (animal and plant derived);
(3) semisynthetic or hybrid materials. The ensuing developments of these biomaterials
have enhanced their utility in health care. Natural polymers are widely used in the
areas of health care for the fabrication of drug delivery systems. As naturally derived
biomaterials have limited mechanical strength, their applications as drug carriers are
restricted. Therefore such materials are being modified chemically to improve their
mechanical properties. Biomaterials for the delivery of drugs or bioactive molecules
are showing newer developments with time. During fabrication of these biomaterials,
a balance between the physical and mechanical properties together with minimal tox-
icity to host tissue must be maintained [1,2]. Complementing synthetic polymers, nat-
urally derived biopolymers are on the way of becoming equally important. However,
the biomaterials must be obtained with sufficient and reproducible purity and quality.
To meet clinical needs in terms of biodegradation, drug loading, and drug release,
natural biopolymers may be endowed with additional functional moieties. Because of
their exceptional biocompatibility, biodegradability, and nontoxic products of degra-
dation, natural polymer-derived materials have been extensively studied in biomedical
engineering [3,4].
Biopolymer-based hydrogels have attracted a great deal of interest in tissue engi-
neering and drug delivery applications [5]. Despite the known advantages and wide
applicability of biomaterials, there are several limitations such as poor mechanical
properties and low stability in aqueous environments that restrict their use for biomed-
ical applications [6,7]. However, the hydrogels possess a wide variety of functional
groups, including hydroxyl, amino, and carboxylic acid groups, which can further
be cross-linked and conjugated with cell-targeting ligands. The naturally occurring
biopolymers are polysaccharides, and typical examples are chitosan, hyaluronic acid,
dextran, pullulan, and alginate. The covalent cross-linkers interconnect molecules,
Biopolymer-Based Composites. http://dx.doi.org/10.1016/B978-0-08-101914-6.00001-6
Copyright © 2017 Elsevier Ltd. All rights reserved.
2 Biopolymer-Based Composites
increase the molecular weight, and generally provide higher mechanical strength and
improved stability. However, cross-linking may also decrease the degradability and the
availability of functional groups in the cross-linked polymer and changes the rheology
of the polymers, leading to subsequent processing difficulties and potential increase
in cytotoxicity [6]. For a widely used cross-linker glutaraldehyde, up to 8% has been
shown to be noncytotoxic [8]. Because individual polymers alone are not sufficient in
providing biomaterials with the desired properties, the use of blends of different poly-
mers has been suggested [9]. For instance, porous collagen/chitosan blend scaffolds
were developed and treated with glutaraldehyde/genipin to improve their mechanical
properties and stability [10,11]. Reduced swelling and decrease in enzymatic degra-
dation were found for collagen and hyaluronic acid composite materials without any
impact on the cell viability [12]. Similar to the binary blends, a ternary composition of
collagen, hyaluronic acid, and poly (caprolactone) was used to generate sponge-like
dense membranes using ultraviolet irradiation and carbodiimide coupling [13]. The
hybrid cross-linking systems were able to preserve the native structure of collagen,
and the inclusion of poly (caprolactone) provided the ability to control the degradation
and mechanical properties. This made the sponges suitable for the development of
wound dressings and periodontal membranes.
Composite materials or composites are engineered materials made up of two or
more constituent materials with significantly different physical or chemical proper-
ties, which remain separate and distinct on a macroscopic level within the finished
structure. Thus composites are always heterogeneous [14]. In any composite, there
are two major categories of constituent materials: a matrix (or a continuous phase)
and a dispersed phase(s). The continuous phase is responsible for filling the volume
as well as surrounding and supporting the dispersed material(s) by maintaining their
relative positions. The dispersed phase(s) is (are) usually responsible for enhancing
one or more properties of the matrix. Most of the composites target an enhancement
of the mechanical properties of the matrix, such as stiffness and strength; however,
other properties, such as erosion stability, transport properties (electrical or thermal),
or biocompatibility might also be of great interest. This synergism produces properties
that are unavailable from the individual constituent materials [15,16]. By controlling
the volume fractions of the dispersed phase, the properties and design of composites
can be varied and tailored to suit the necessary conditions. Higher volume fractions
of reinforcement phases tend to improve the mechanical properties of the compos-
ites. The uniform distribution of the dispersed phase is also desirable, as it imparts
consistent properties to the composite [15,16]. In general, composites might be sim-
ple (homogeneous dispersion of one dispersed phase throughout a matrix), complex
(homogeneous dispersion of several dispersed phases throughout one matrix), graded
(inhomogeneous dispersion of one or several dispersed phases throughout one matrix),
or hierarchical. A hierarchical composite refers to those cases in which fine entities of
either a simple or a complex composite are somehow aggregated to form coarser ones
(granules or particles), which afterward are dispersed inside another matrix to produce
the second hierarchical scale of the composite structure [17]. To prepare any type of
composite, at least two different materials must be mixed. However, the interfacial
strength among the phases is a very important factor, because lack of adhesion among
