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326 S. Gul et al.
compression. The process involves rolling a resin film with added fibers,
compressing it into a composite sheet, and then processing it in a press to obtain
the intended shape (Mao et al.
2018). The compression moulding method offers
advantages like ample production capability, consistent part quality and rapid cycle
durations. However, optimizing pressure is crucial to prevent fiber or structural
damage (Mokhena et al. 2018).
Resin Transfer involves placing fibers inside a mould with two solid components
while a tube delivers liquid resin into the mould under low pressure, impregnating
the fibers (Barari et al. 2016). After curing at or above room temperature, the product
is collected when the mould is opened. This method efficiently produces intricate,
high-quality components on a large scale. Various types of low-viscosity resins like
can be utilized in this process (Quero et al. 2010).
Injection Moulding is highly regarded as the optimal method for composite
manufacturing due to its ability to produce intricate geometries and precise features.
It results in items boasting exceptional surface quality and exact dimensional
precision, all achieved with swift production rates and minimal labor expenses
(Wang et al. 2017). Studies in the literature related to the preparation methods,
advantages, and use areas of cellulose composite-based biomaterials are shown in
Table 13.1.
13.3.2 Chitin-Chitosan Composite-Based Biomaterials
Despite being scientifically proven to be biodegradable, biocompatible, non-toxic,
non-allergenic, and bioadhesive (Tao et al.
solubility, depending on pH, are essential disadvantages. To overcome these issues,
thanks to its abundant active hydroxyl and amino groups, researchers have used
various methods to change the solubility and activity of chitosan by modifying it
(Qin and Li 2020). Biomaterials prepared with chitosan have been used in many
studies in the literature. Li et al. (
2019)
antimicrobial films made of chit osan, polyvinyl alcohol, and methacryloyloxyethyl
trimethyl ammonium chloride (DMC) through ultrasonic treatment, demonstrating
that ultrasonication improved the mechanical properties, light transmittance, and
barrier properties of the films, with a 2% methacryloyloxyethyl trimethyl ammonium
chloride concentration showing strong bactericidal effects on S. aureus and E. coli
(Li et al.
2019).
Using microwave technology, Kumar et al. (2023) synthesized
chitosan and polyethylene glycol hydrogel membranes containing curcumin. The
membrane had high swelling, low degradation, and sustained drug release, leading to
enhanced mechanical properties and faster wound healing in vivo, suggesting its
suitability for therapeutic approaches for wound healing (Kumar et al. 2023). Beer
et al. (2020) investigated the enzymatic breakdown of chitosan into a water-soluble
form that interacts with lignin, using cellobiose hydrolase to hydrolyze chitosan and
2020), its low mechanical strength and
focused on preparing and characterizing
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 327
He et al.
Kargarzadeh
et al. (2018)
Food, medicine, chemical, and
other related industries
Better biological
compatibility and
(2021)
release of hydrophobic anticancer
Precise delivery and controlled
Targeted and triggered
drug delivery
antibacterial properties
medications for cancer treatment
in biomedical contexts.
Oldal et al.
(2023)
Drug delivery systems, support
structure for tissue regeneration,
air purification, and selective
uniformity of the
Evaporation process
and improved the
Anirudhan
ystems
elivery s
membrane configurations.
Drug d
nanofibers
Regulated release of
et al. (2021)
curcumin for cancer
therapy.
Composite type Preparation Advantages Usage areas of the method References
Chitosan-cellulose composite Dissolving the components in an
Table 13.1 Some studies on cellulose composite based biomaterials
The dimensions and shape of drug-
acidic solution & completely
dispersed.
Folate-decorated reductive-
CLSM,
features of the
revealing the
using DLS, SEM, and
loaded FA-RCNCs were assessed
responsive
fabricated nano-capsules.
Tetrabutylammonium bromide
salts and sophorolipid-based
bio-surfactants were used as a
solvent which increased the
spinnability of cellulose acetate.
carboxymethylcellulose-based
nanocapsules (FA-RCNCs)
Electrospinning cellulose acetate
nanofibers
Fabricated a drug administration
system utilizing nano cellulose to
enhance the delivery efficiency of
curcumin, employing acid-alkali
treatment on cellulose.
Folic acid conjugated nano
cellulose
328 S. Gul et al.
laccases to oxidize lignin, forming stable covalent lignin cross-linked chitosan
hydrogels (Beer et al.
2020).
13.4 Drug Delivery Applications of Cellulose, Chitin,
and Chitosan Composite-Based Biomaterials
Cellulose, a long-standing presence in pharmaceuticals, is often blended with
excipients to create tablets for oral drug administration (Wilson et al.
researches have brought to light the versatile and promising role of cellulose in drug
delivery applications (Ramezani et al. 2024). Notably, cellulose composite
biomaterials have been successfully employed to enhance the oral bioavailability
of drugs, develop controlled delivery systems, increase drug loading capacity,
program pH-sensitive release behavior, and target drug and controlled release
systems (Ul-Islam et al. 2023). Chitosan composite biomaterials, on the other
hand, have been thoroughly researched as drug delivery systems by virtue of their
pH-responsive release mechanism, which enables specific drug administration and
controlled release systems (Omrani et al. 2023). A summary of the studies in the
literature on the implementation of cellulose, chitin, and chitosan composite-based
biomaterials in drug delivery utilization is provided in Table 13.2.
2017). Recent
13.5 Advantages and Disadvantages
Despite its abundance, cellulose has limitations in processing; it is not amenable to
methods like injection moulding technique or melt extrusion due to its high melting
temperature, likely above its thermal decomposition temperature (Amiri et al. 2020).
Moreover, many solvents cause swelling but do not dissolve cellulose, necessitating
strong dipolar characteristics for solvent dissolution (Kostag and El Seoud
Chitosan, on the other hand, with its distinctive traits, is a versatile material with
wide applications in diverse areas, for instance, biotechnology, water purification,
cosmetics, food, pharmacy, and agricolation (Mıyazakı et al. 1981). However, its
limited solubility and mechanical properties constrain its biomedical application
(Desai et al. 2023). Chitosan is esteemed in the biomedical domain for its low
immunogenicity, robust biological compatibility, and widespread availability
(Dimassi et al. 2018). Modification techniques can enhance its solubility and generate derivatives with improved properties, expanding its potential applications.
Chitosan-based nanocomposites demonstrate enhanced mechanical durability and
heat transfer capabilities, and antimicrobial attributes in contrast to chitosan (Kumar
et al.
2023). However, its limited water solubility hampers its biological functional-
ity, exclusively under corporal surroundings, where it is weakly dissolved and
poorly absorbed (Husain et al. 2017; Snyman et al. 2002). This can be handled, by
the chitosan is combined with another compound enhances its water solubility and
broadens its therapeutic applications (E. M. Ahmed 2015).
2021).
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 329
al.
Pattnaik et al.
Sun et al.
(2019b)
(2015)
Wilson et al.
(2017)
Hegyesi et al.
(2017)
(2019)
Hong et al.
(2019)
(2019)
Anirudhan
et al. (2021)
release, and
drug-loading
Busuioc et
(2023)
egrees, well stability
welling d
(continued)
swelling and release rates in
phosphate buffer solutions(pH 6.8
Diclofenac sodium Controlled-release drug carrier The beads exhibited increased
and 7.4) compared to pH 1.2,
effectively preventing abrupt
releases.
temperature more release
Dermal delivery When it is higher than body
polyvinyl
(HPC) and methyl cellulose (MC)
pyrrolidone
Theophylline (99%) Controlled-release drug carrier Especially hydroxypropyl cellulose
well drug release properties
Creating pellet for Tablet coating Better densification and
deformability
and
hydrochlorothiazide
Alfacalcidol Controlled-release drug carrier Well loading and sustained release Yan et al.
antibiotic release.
Theophylline Controlled-release drug carrier Well release behavior depends on pH Xu et al.
Resulting in high
capacity, sustained
cancer treatment
Curcumin Controlled-release drug carrier for
pH-responsive behavior
High s
and antibacterial activity
on drug delivery,
transdermal drug delivery
Curcumin Carrier
@C/carboxymethyl
4
O
3
Fe
cellulose/chitosan beads
Composites Drug Used Role Results References
Table 13.2 A precis of utilization of cellulose, chitin and chitosan based-composites in therapeutic administration
Alfuzosin hydrochloride Ethyl cellulose-
cellulose
Hydroxypropyl methylcellulose,
hydroxypropyl cellulose,
hydroxyethyl cellulose and methyl
Microcrystalline cellulose Enalapril-maleate
Amphifilic bacterial cellulose-
Alginate beads
Carboxymethylated nanocellulose Ciprofloxacin Controlled-release drug carrier Highly effective in prolonging the
Cellulose nanocrystal and chitosan
composite hydrogel
Nano cellulose glycidyl
methacrylate/ hydroxyethyl
methacrylate (HEMA) /ethylene
cellulose–polyvinyl
glycol dimethacrylate (EGDMA)
alcohol based complex composite
Bacterial
membranes
330 S. Gul et al.
Guo et al.
(2017)
properties, increased mechanical
properties and stability, and more
sustained drug release
Carrier in drug delivery Evaluated stability and drug-release
2024)
Sankarganesh
et al. (
biodegradable nature, and
compatibility with living tissues.
Excellent capacity to retain moisture,
Dressings tailored to address
diverse wound types, including
those stemming from cancer
treatment.
Parvaneh et al.
(2023)
environmentally friendly; sustained
release of anticancer drugs
(2022)
Phan et al.
Resulting sustained release, and
pH-responsive behavior
mouth
(2023)
Yari et al.
enhances drug encapsulation and
A carrier for oral drug delivery Increased porosity significantly
diffusion kinetics; pH-responsive
effectively regulates controlled
release in some body fluids via
Farhadnejad
behavior
et al. (2022)
consistently and sustainably,
in the stomach.
excellent adhesion to the stomach
lining and prolonged retention time
Rui et al.
(2023)
pronounced cytotoxicity
(2022)
al.
et
Used Role Results References
Cellulose/alginate beads Metformin
Composites Drug
Table 13.2 (continued)
hydrochloride
Cellulose-PVA blended hydrogels Streptomycin/
curcumin
Curcumin A pH-responsive nano-carrier More biocompatible, cheaper, and
Carboxymethyl cellulose/starch/
Insulin A carrier to administer through the
reduced graphene oxide composite
Alginate-chitosan core-shell
hydrogel
hydrogel beads
Metformin
nanoparticles
Chitosan/polyvinyl alcohol porous
composite
Famotidine A carrier for oral administration Having the ability to release drugs
Montmorillonite-Famotidine/
Chitosan Bio-nanocomposite
Hydrogels
Methotrexate Drug delivery for cancer treatment Good biocompatibility and
Carboxymethyl chitosan and
oxidized pullulan
Doxorubicin Drug delivery systems pH-sensitiveness; induced toxicity Amiryaghoubi
Chitosan-folate hybrid magnetic
nanoparticles
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 331
l.
t a
Sun et al.
Aljohani et al.
(2023)
Amiri e
(2019a)
biodegradability
mechanic properties
(2020)
Higher antibacterial activity;
decreased cytotoxicity
Silver Wound dressing Good antibacterial effect; suitable
5-fluorouracil A carrier for colon-specific release Excellent pH-sensitivity and
Polyethylene oxide nanofibers
ZnO/carboxymethyl cellulose/
chitosan bio-nanocomposite beads
immobilized with silver
nanoparticles stabilized by chitosan
healing
Chitosan-PEO nanofibers Teicoplanin A carrier drug delivery and wound
332 S. Gul et al.
Interestingly, blending also introduces new characteristics to chitosan, facilitated
by its unique structure, which allows for various reactions like phosphorylation,
crosslinking, and complexation (Kumar et al.
modifications lead to derivatives with adaptable biological and chemical properties,
including enhanced bioactivity and DNA complexing capabilities (Sarmento et al.
2011). Chitosan also exhibits antibacterial properties, damaging bacterial cell
membranes and preventing plaque formation (Dilamian et al.
safe for mammals, it demonstrates a diverse array of antibacterial functions.
Chitosan and its derivatives hold promise for biomedical innovations, benefiting
from their diverse characteristics and potential utility in healthcare (Husain et al.
2017).
Despite being crucial to tissue engineering, scaffolds often have weak mechanical
properties, which can be significantly improved. Chitosan is extensively utilized as a
wound-healing material to promote wound mending and prevent contamination,
although some cytotoxic effects have been observed, necessitating further research
to minimize toxicity (Chen et al. 2008; de Sousa Victor et al. 2020). Despite
thousands of research studies in recent decades, the complete capability of chitosan
on biomedical utilization still needs to be explored, with many unresolved
challenges. Chitosan-based nanoparticles show promise as multifunctional drug
carriers with good biocompatibility and easy modifiability (de Sousa Victor et al.
2020). However, a systematic approach is needed to address issues related to drug
delivery selectivity, adverse effects on living organisms, safety, and synthesis
methods for cellulose, chitin-chitosan-based biomaterials. Using the advantages of
these natural biopolymers to prepare their composites suitable for drug delivery may
be the best way to overcome all these challenges. Undoubtedly, these will have some
benefits and drawbacks that should not be ignored (Table 13.3).
In summary, cellulose, chitin, and chitosan composite-based sustainable
biomaterials offer numerous advantages for drug delivery applications. However,
they also present certain limitations and challenges that must be addressed through
further research and development efforts. With ongoing advancements in material
science and engineering, these biomaterials are promising to revolutionize drug
delivery and sustainably improve patient outcomes.
2023; Qin et al. 2020). These
2013). While generally
13.6 Future Perspectives for Cellulose, Chitin, and Chitosan
Composite-Based Sustainabl e Biomaterials
Drug delivery has witnessed remarkable advancements over the years, with a
growing emphasis on sustainability and biocompatibility. In this context, cellulose,
chitin, and chito san composite-based biomaterials have shown great potential as
candidates for revolutionizing therapeutic delivery systems. This chapter delves into
the future perspectives of utilizing these biomaterials in drug delivery, exploring
their potential, challenges, and opportunities for sustainable healthcare solutions.
Cellulose, chitin, and chitosan possess unique properties conducive to drug
delivery applications. As a renewable and biocompatible material, cellulose provides
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 333
Table 13.3 Advantages and disadvantages of cellulose, chitin-chitosan based composites
Advantages References
Biocompatibility Cellulose, chitin, and chitosan are biologically
suitable, indicating that they are well-received by
organisms and exhibit minimal adverse reactions.
Petrova et al. (2023)
and Sanmugam et
(2023)
al.
They give biocompatible composites.
Renewable and
sustainable
Their sustainable sourcing coordinates to
flourishing requirement for environmental
the
Parvaneh et al. (2023)
and Song et al. (
2022)
substances in healthcare.
Biodegradability This property reduces the peril of longstanding
accumulation and toxicity, enhancing the safety
Kim et al. (2023) and
Song et al. (2022)
profile of drug delivery systems.
Tailored drug
release
This allows for precise modulation of drug release
kinetics, ensuring optimal therapeutic outcomes
Leonard et al. (2023)
and minimizing side effects.
Targeted
delivery
Chitin and chitosan exhibit mucoadhesive
characteristics, facilitating the accurate
administration of medications to particular areas
Leonard et al. (2023)
and Parvaneh et al.
(2023)
within the human body. This enhances drug
localization and uptake at the desired site of
action, improving treatment efficacy and reducing
systemic exposure.
Disadvangates References
Limited
mechanical
strength
Complex
fabrication
process
Pure cellulose, chitin, and chitosan materials may
have limited mechanical strength. Reinforcement
strategies or composite formulations may
necessary to
overcome this limitation.
be
The fabrication of cellulose, chitin, and chitosanbased drug delivery systems often involves
complex processing techniques such as solvent
Said et al. (2023)
Murugan et al. (2021)
casting, electrospinning, or 3D printing. These
processes may require specialized equipment and
expertise, leading to higher production costs and
scalability challenges.
Variable drug
loading capacity
Potential
immunogenicity
Achieving consistent and high drug loading
efficiencies
may require
optimization of
formulation parameters.
While cellulose, chitin, and chitosan are generally
considered biocompatible, there is a possibility of
immune responses or allergic reactions in some
Khalili et al. (2024)
and Trzeciak et al.
(2021)
Morishima and
Bokuda (2021) and
Peng et al. (2022)
individuals. Pre-trial and clinical investigations
are imperative to evaluate the antigenicity and
protection profiles of these biomaterials for drug
delivery purposes.
Regulatory
hurdles
Compliance w
ith regulatory s
tandards and
guidelines can pose challenges for product
development and commercialization.
Beheshtizadeh et
(2022) and Peng et al.
(2022)
al.
334 S. Gul et al.
a stable matrix for drug encapsulation and sustained release (Zhang et al. 2021).
Chitin and chitosan offer inherent mucoadhesive properties, facilitating targeted
delivery to speci fic sites within the body (Bhattarai et al.
biodegradability ensures minimal adverse effects and enhanced biocompatibility,
aligning with the principles of sustainable healthcare (Mushtaq et al. 2017).
Future Directions and Opportunities
1. Enhanced Biocompatibility: Future research endeavours aim to augment the
biological compatibility and bioactivity of cellulose, chitin, and chitosan
composites through surface modification and functionalization. These composites
can exhibit improved cellular interactions and tissue-specific targeting by
incorporating bioactive molecules and targeting ligands, thereby optimizing
drug delivery efficacy (Gaur et al.
2. Controlled Release Systems: Developing advanced drug delivery systems based
on cellulose, chitin, and chitosan composites holds promise for achieving precise
control over drug release kinetics (Leonard et al. 2023). Future efforts may focus
on designing stimuli-responsive materials capable of triggered discharge in replay
to significant physiologic clues, for instance, acidity levels, thermal conditions, or
enzymatic performance. Controlled release systems can optimize therapeutic
results, mitigate side effects, and enhance patient adherence.
3. Personalized Medicine: Cellulose, chitin, and chitosan composites’ adaptability
allows for the customization of drug delivery systems to meet individual patient
needs (Yang et al. 2022). Future developments may involve 3D printing’s
assimilation to create personalized implants, scaffolds, or drug-eluting devices
(Ahmed et al. 2021). By tailoring drug delivery systems to patient-specific
requirements, personalized medicine can be realized, offering improved treatment
outcomes and healthcare efficiency.
2023).
2010). Moreover, their
Challenges and Considerations
Despite the promising prospects, the full realization of cellulose, chitin, and chitosan
composite-based drug delivery systems hinges on effectively addressing several
challenges. These include optimizing composite formulations for specific drug
properties, ensuring long-term stability and efficacy, and addressing regulatory
issues for their development into products for clinical use. Moreover, scalability
and cost-effectiveness remain critical factors in the widespread adoption of these
sustainable biomaterials in drug delivery applications.
13.7 Conclusion
Cellulose, chitin, and chitosan are inexhaustible and worthwhile biopolymers
gaining significance as sustainable alternatives to synthetic polymers. Their structural similarities and functional groups allow for the formation of nanocomposites
with diverse shapes like fibers, films, and hydrogels, primarily through biopolymer
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 335
solution mixing for drug delivery. The composition and properties of
nanocomposites can be tailored by adjusting precursor concentrations, with cellulose
often reinforcing mechanical strength. Chitin and chitosan, prized for their biological
activity, find applications in biomedicine and food packaging. Cross-linking and
derivatization further modify nanocomposites properties, though challenges like
polymer degradation and reduced dissolution must be ma
nance. Collaborative research across disciplines can leverage the unique
naged for quality mainte-
properties
of these biopolymers to develop innovative drug-delivery solutions that address
unmet medical needs and contribute to a more sustainable healthcare system.
Green chemistry principles like process optimization, eco-friendly solvents and
chemicals, solvent recyclability, and academia-industry collaboration should be
ote s
embraced in a composite to prom
ustainability.
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