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International Journal of Polymeric Materials and
Polymeric Biomaterials
ISSN: 0091-4037 (Print) 1563-535X (Online) Journal homepage: http://www.tandfonline.com/loi/gpom20
Nanostructured chitosan composites for cancer
therapy: A review
Kalyani Prusty & Sarat K Swain
To cite this article: Kalyani Prusty & Sarat K Swain (2017): Nanostructured chitosan composites
for cancer therapy: A review, International Journal of Polymeric Materials and Polymeric
Biomaterials, DOI: 10.1080/00914037.2017.1393678
To link to this article: http://dx.doi.org/10.1080/00914037.2017.1393678
Accepted author version posted online: 20
Oct 2017.
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Download by: [University of Florida]
Date: 25 October 2017, At: 23:04
Nanostructured Chitosan Composites for Cancer Therapy: A Review
Kalyani Prusty1, Sarat K Swain1,*
1
Department of Chemistry, Veer Surendra Sai University of Technology, Odisha, India
CONTACT Sarat K Swain swainsk2@yahoo.co.in
Abstract
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The unique characteristics of nanostructured chitosan composites provide a higher
affinity for negatively charged biological site-specific targeting in delivery of drugs. The
therapeutic applications of nanostructured chitosan composites in various types of
cancers such as melanoma cancer, bladder cancer, breast cancer, lung cancer, colon
cancer, pancreatic cancer, metastatic cancer and prostate cancer are focused. Herein,
nanostructured chitosan composites are potential vehicles for controlled drug release of
drug. The therapeutic applications of nanostructured chitosan in safe delivery of cancer
drugs in the present review may explore a new dimension in the area of biomedical
applications of chitosan derivatives.
Graphical Abstract
1
KEYWORDS: Cancer therapy; Chitosan; Nanostructured materials; Biocompatible;
Drug vehicles
1.
INTRODUCTION
The usage of nanotechnology for biomedical research is probable to have a major
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influence leading to the development of new types of diagnostic and therapeutic tools [1,
2]. A nanoparticle has attracted great attention for diagnostic and therapeutic tools due to
their unique properties [3]. The steps of development of drugs delivery systems that can
target to specific body sites are reduced the period of time for release of drugs, when
nanostructured materials are involved. Nanomaterials can be used as a reinforcing agent
to improve the properties of polymers and biopolymers [4]. Biopolymer has more
importance because of their biodegradable and biocompatible nature. The natural
biopolymers such as starch, chitosan and cellulose etc. have special feature in biomedical
applications. Among these, chitosan is biodegradable, biocompatible, and non-toxic
polymer. Chitosan is a deacetylated modification of chitin which is the most abundant
natural amino polysaccharide and is estimated to be produced annually almost as much as
cellulose [5]. Several common nanoparticles like boron nitride, silicon carbide, nano clay,
calcium carbonate are used as reinforcing agents for enhancing the stability, resistant and
biomaterial nature of chitosan. Hence, Chitosan is a nontoxic natural polymer which is
harmless to the human body containing basic groups. Human cells generally have a
predominantly negative charge on their surfaces, thus they follow strongly to substrates
with basic groups such as chitosan. Chitosan is a non-toxic, antibacterial and antifungal
2
biopolymer which gains its stability, barrier and chemical resistance properties with
incorporation of nanostructured materials without compromising its biodegradable and
biocompatible behaviors. Despite its biodegradability, it has many reactive amino groups;
those offer possibilities of interaction with nanostructured materials with formation of a
large variety of composites.
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Most of the drugs have problems of poor stability, water insolubility, low selectivity, high
toxicity, side effects [6]. Hence, drug carriers such as nanostructured chitosan composites
play an important role in solving these problems. Further, because nanostructured small
size, it is capable of passing through biological barriers. Nanostructured chitosan
composites can be widely used as a carrier the therapeutic molecules in delivery systems
[7, 8]. Min et al. developed that glycol incorporated nanostructured chitosan encapsulated
camptothecin drug, which improves the drug stability and tumor targeting in cancer
therapy [9]. In case of cancer therapy, the viral vectors are effective with high
transfection efficacy but it has drawbacks as properties of toxicity, carcinogenicity,
biosafety and immunogenicity. The non-viral vectors like chitosan are advantageous due
to its nature of biocompatibility, biodegradability and low toxicity. But, the transfection
efficacy of chitosan in cancer therapy is low due to its less stability. The modification of
chitosan with reinforcement of nanostructured materials may enhance its transfection
efficacy without disconcerting its biocompatibility and biodegradability.
Chitosan is composed from arbitrarily dispersed α-(1-4)-linked D-glucosamine
(deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). Chitosan derivatives
3
are arises from partial deacetylation of chitin. Chitins are the best abundant nitrogenbearing organic compound and are the second most existing polysaccharide. These
biopolymers are produced by a huge number of living organisms. Chitins are mostly
crystalline micro fibrils structural components nature and it can be found from
exoskeleton of arthropods or in the cell walls of fungi and yeast. Further it is found
formed other living organisms in the lower plant and animal kingdom. Hence, chitin and
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chitosan is same polymer but different degree of deacetylation (DD). However, the
degrees of deacetylation are main factors to determining the characteristics of chitosan.
So N-deacetylation of chitin is main derivatives of chitosan as shown in Scheme 1.
Chitosan are mainly used if DD is more than 40%. These chains are completely insoluble
in water when DD is less than 40% due to H-bonds between alcohol, amide and ether
functionalities distributed on the repeating units along the polymer chains and
hydrophobic interactions and also due to the presence of methyl groups of the acetamide
functions and to the –CH and –CH2 of the glucosidic rings [10–12]. If DD is more than
40% then chitosan becomes soluble in acidic solution. Chitosan is a bio macromolecule
having good porous, environmental friendly, non-toxic in nature. The strength and
stability of chitosan is a drawback of using chitosan as alone while chitosan is reinforced
with other nanomaterials, its strength [13], stability [14], barrier [15] and resistance [14]
are enhanced.
The carcinogenic growth of cells cause cancer in which the cells divide without normal
limitations, attack and destroy adjacent tissues and spread to distant anatomic sites
4
through a process named ‟metastasis” a major cause of death of cancer. As per World
Health organization, cancer is an important cause of death worldwide. Cancer may be
formed by interaction between healthy cells and physical carcinogens like ultraviolet
(UV) and ionizing radiation; chemical carcinogens such as asbestos and tobacco smoke;
and biological carcinogens such as infections by virus and contamination of food by
mycotoxins. The primary methods of cancer management are chemotherapy,
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radiotherapy and surgery. Hormonal therapy and immunotherapy are recently used
increasingly but their applications are limited for a few cancer types such as breast
neoplasis. Chemotherapy is that methods in which the cytotoxic drugs to kill cancerous
cells remains the most common method for cancer treatment. Normally, cytotoxic drug is
very toxic but poorly specific, and can’t differentiate between normal and cancer cells.
Hence predictable chemotherapy administrations have been displayed to produce side
effects. But in systematic administration, cytotoxic drugs are widely transported to the
whole body. Hence small fraction of the drugs are reached to the tumor site and other
healthy organs or tissues can be affected or damaged by the nonspecific action of the
cytotoxicity agents [16] . Drugs are commonly loaded in to microsphere through passive
absorption method whereas microspheres can be added to drug solution [17]. Micro
particulates (microcapsules or microspheres), implants are designed by the process of
sustained release injectable formulations [18]. Nanostructured chitosan composites are
mostly used due to their mucoadhesive, biocompatible, biodegradable and antibacterial
properties [19].
5
Although number of reports are available regarding the use chitosan in cancer
therapy, however the therapeutic treatment of various types of cancers by nanostructured
chitosan composites are scanty. From the literature, publications relevant to the cancer
therapeutic applications involving ‘nanostructured chitosan’ and ‘nanostructured chitosan
for cancer therapy’, it is found that, the research regarding the investigation of
‘nanostructured chitosan’ is plenty but applications in cancer treatment are scanty. The
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importance of biomedical applications of nanostructured chitosan composites has been
progressing in last few decade. Present review gives the focus on the therapeutic
applications of various types of cancers by nanostructured chitosan composites. The
emphasis is made on the delivery of drugs in different types of cancer such as melanoma
cancer, bladder cancer, breast cancer, lung cancer, colon cancer, pancreatic cancer,
metastatic cancer and prostate cancer where nanostructured chitosan composites are
behaved as the potential vehicles. The comparative study of different cancer drugs
encapsulation with chitosan composites is also established. In this review paper,
numerous number of findings are described with a clear emphasis on role of
nanostructured chitosan composites in the delivery of drugs for various types of cancer
treatment.
2.
APPLICATIONS CHITOSAN NANOPARTICLES IN CANCER
THERAPY
The nanostructured chitosan composites are prepared by incorporation of nanomaterials
with chitosan matrix. Nanomaterials may be chemically modified to improve the
compatibility with chitosan. The therapeutic drugs are encapsulated with nanostructured
6
hybrid chitosan for its release in cancer affected parts [20]. Various drugs with
encapsulation by chitosan are selected for therapeutic treatments of different cancers are
represented in Table 1. Different methods of delivery of cancer therapeutic drugs with
nanostructured chitosan are also included in this table. It is found that, various anticancer
drugs are delivered either by in vitro or by in vivo or by both. Different drugs are
encapsulated by chitosan composites with reinforcement of various nanostructured
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materials are summarized in Table 2. It is noticed that, layer nanostructured materials like
nanoclay, layer double hydroxide, graphene oxide are potential reinforcing materials in
chitosan composites for carrier of various anticancer drugs. The nanorods of novel metals
like gold and silver are also impacting a substantial effect on chitosan to enable its
application in drugs delivery. From Table 2, it is also obtained that, the nanostructured
oxides; sulfide and phosphate of transition metals are behaved as suitable filler in
chitosan composites towards anticancer drugs delivery. Nanoparticles are recognized as
foreign matter in vivo and are absorbed by antibodies generated in the human body.
Nanoparticles with polarity and high surface potential as well as hydrophilic character
have a longer circulating time in vivo.
Further, nanostructured chitosan composites are suitable potential vehicle for
drugs delivery in cancer treatment. Various drugs can be delivered by nanostructured
chitosan composites for treatments of different cancers such as melanoma cancer, bladder
cancer, breast cancer, lung cancer, colon cancer, pancreatic cancer, metastatic cancer and
prostate cancer. Therapeutic applications of nanostructured chitosan bionanocomposites
in treatment of various types of cancers are schematically represented in the scheme 2.
7
Functional groups of chitosan interacts with the polar groups of the nanostructured
reinforcing materials for the formation of chitosan composites those are the potential
hybrid materials to act as a suitable drugs carrier. The cancer therapeutic drugs are
encapsulated in the pores of the chitosan nanocomposites by which these can be targeted
to be delivered to the cancer patient. Drugs are specific for treatment of particular types
of cancers. The scheme 2 is illustrated the explaining of the active participation of the
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nanostructured materials in therapeutic applications in various kinds of cancers. Different
kinds of cancers are graphically represented for the better understanding the role of
nanostructured chitosan composite vehicle as the perfect biocompatible materials in
delivery of respective drugs.
2.1 Melanoma Cancer
Melanoma present in epidermal and melanocytes of the skin. This is also found in
pigmented ocular structure soft brain films genital mucosa and mouth. Melanoma cancer
has been increasing globally and enhancing the death rate, day by day. The treatment of
melanoma cancer includes chemotherapy, radiotherapy, biological therapy and surgery.
These treatments have severe side effect which may develop the death of the patient even
after treatment. Hence it is necessary to design less toxic biomaterials like nanostructured
chitosan composites to fight against melanoma cancer. Melanoma is the most dangerous
type of skin cancer with high mortality rate. Chemotherapy is the best conventional
therapeutic method for melanoma cancer. It kills both normal cells and wicked cells that
are present in division [48]. So, it is very toxic and it limits the uses of chemotherapy
occurred in melanoma cancer. Chitosan is a nontoxic biomaterial with less immune
8
character. The most chemotherapeutic agents used in melanoma cancer are DTIC,
Vinblastine, and temozolomide having 7%, 9.5%, and 28% respectively in a clinical trial
with 64 patients [49]. The chemotherapeutic agents are delivered by gold nanoparticles
with DOX is very efficient against a melanoma cell line reported by Zhang et al. [50].
Kottaschade et al. studied about the phase II clinical treatment using nab-PTX and
carboplatin in 41 chemotherapy-native and 35 previously treated melanoma patients [23].
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Liu et al. reported that camptothecin encapsulated N-trimethyl chitosan is better than the
free CPT due to its insolubility nature [21]. Nanostructured chitosan loaded drugs for
melanoma cancer therapy are represented in Scheme 3. It is assumed that, the drug such
as doxorubicin (DOX) is encapsulated with nanostructured chitosan which contains
positive basic groups. Positive charges on the chitosan backbone may give rise to a strong
electrostatic interaction with the negatively charged mucosal surface during release of
drugs.
2.2 Bladder Cancer
Bladder cancers are generally found in malignancies and these are the highest occurrence
rate of world wide. Bladder cancers have been increasing globally and enhance the death
rate day by day which causes the largest number of tumor nodules from the bladder wall.
The treatment of bladder cancer includes surgery, chemotherapy, and radiotherapy etc.
Out of these treatments, Chemotherapy may be different type’s methods but intravesical
chemotherapy is one of the methods in which it includes instillation of one or more
chemotherapy agents through a catheter into the bladder. But the major limitations of this
treatment is the rapid and almost complete washout of the drugs from the bladder on first
9
voiding of urine and the low exposure of the tumor sites to the chemotherapeutic agents
[51, 52]. Hence, it is required to develop mucoadhesive and sustained drug delivery
systems which can prolong the swelling time of the drug and increase drug uptake into
bladder tissue. So it can increase the efficiency of the drug treatment. These treatments
have serious side effect which may lead to the death of the patient after treatment. Hence
it is necessary to design less toxic biomaterials to fight against bladder cancer. Chitosan
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is a nontoxic biomaterial with less immune character and well known bio adhesive nature
due to the electrostatic interactions of their amino groups with negatively charged mucin
in the mucus layer [53, 54]. So these covalent bonds established need to be stronger than
non covalent interactions like hydrogen bonds, Vander Waals forces, and ionic
interactions of chitosan with anionic substructures of the mucus layer [55, 56].
The treatment of bladder cancer includes Immunotherapy, chemotherapy, radiotherapy
like bacillus colmette-guerin, mitomycin C, paclitaxel, or cisplatin and surgery. In
bladder cancer, sometimes may be treatment failure occurred due to the short residence
time of drugs in the bladder. The mechanism is that, when drugs are instilled by the
residual urine then collapse occurs to sustain an exposure of drugs inside the bladder.
This is because, the drugs are normally maintained intravesical for 2h and they rarely last
beyond the first rejection of the urine after instillation [57]. The low permeability of
drugs into the bladder wall creates hindrance due to the presence of urethelium. So
polymeric nanoparticles are generally used and these are generated from materials such
as biopolymers, lipids and synthetic biodegradable materials. Generally amphilic
copolymers are used as drug carriers for controlled drug release to increase the drug
10
residence time. Out these, chitosan is one of the biopolymer which attractive permeability
of drugs through the urethelium due to their electrostatic interaction between basic amino
groups with negatively charged mucin in the mucosal surface [58, 59].
2.3 Breast Cancer
Breast cancers are generally found from breast tissue. It is almost second most cause of
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cancer-related deaths in women from all over the world [60]. The symptom is generally
found from at the early stage hence the most of the patients are diagnosed. But in later
stage, there is a chance for the cure of cancer [61, 62]. The symptoms of the breast
cancers are fluid coming from the nipple, dimpling of the skin and change in breast shape
and the red scaly patch of skin. Tumorectomy, chemotherapy and radiotherapy and
hormone replacement therapy are the treatment of breast cancer. However, it is not useful
effective therapy for patient with metastatic disease [63]. Hence these symptoms are
required for the development of new and more specific therapies. Hence it is necessary to
have the strategy of less toxic biomaterials to fight against breast cancer. Out of these
biomaterials, chitosan is the best favorable shell material due to its biocompatibility,
biodegradability, less immune character and nontoxic. In order to study the cationic
nature of chitosan enhances membrane adhesion, as well as membrane permeability
which are important in drug delivery applications [64]. Polymeric nanoparticles are
classified into two types, such as hollow and core-shell nanoparticles [65]. In the case of
hollow nanoparticles, drugs are either encapsulated in their highly porous polymer matrix
or conjugated with the polymers. That is why; chitosan and PLGA are the most broadly
used polymers for hollow nanoparticles [64, 66, 67]. But core-shell nanoparticles consist
11
of two parts such as the core and the shell which are prepared from different polymers.
Silica-coated chitosan nanoparticles are examples of core-shell nanoparticles [68].
PMMA/chitosan core-shell nanoparticles [69] and chitosan coated poly (lactic-coglycolic acid) (PLGA) [70].
2.4 Lung Cancer
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Lung cancers are generally caused in persons ordinarily who smokes cigarettes. Lung
cancers are mainly prevented due to beta carotene and vitamin-A as per laboratory
studies and epidemiologic observations. The Beta-carotene and retinal efficacy trials
(CARET) are the several recent trials to assess the chemo preventive efficacy. Lung
cancer is demonstrated in two forms such as SCLC (small cell lung carcinoma) and
NSCLC (non-small cell lung carcinoma). SCLC represents 13% lung cancer but NSCLC
represents metastatic disease form and these are identified by both distant and local
cancer cells into lungs and organs. At an early stage lung cancer patients can be cure by
Tumor resection and radiation treatments. This is happening only due to deficiency in
early stage diagnostics. Most of the lung cancer occurs at an advanced stage with local
tumor invasion or distant metastasis and it is not suitable for surgery. Hence
chemotherapy, radiotherapy and surgery are the treatments for lung cancer. This
treatment has serious side effect which may develop the death of the patient after
treatment. Hence it is necessary to design less toxic biomaterials to fight against lung
cancer. Chitosan is a nontoxic biomaterial with less immune character. When a
nanomaterial is incorporated in chitosan the stability, resistance and strength of chitosan
are increased for which, it becomes a good drugs carrier for the treatment lung cancer.
12
Arora et al. studied a labeled free electrochemical immune sensor for detection of lung
cancer by using carbon nanotube hybrid chitosan [71]. In that work, functionalized
SWCNTs (single walled carbon nanotubes) are used for preparation of hybrid chitosan
gels and electrodes are fabricated by drug casting method on to graphite surface. In
another study, the epidermal growth factor receptors targeted chitosan system is
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developed for silencing the Mad-2 genes which is a strategy to reduce cell death in lung
cancer cells [72]. Mad-2 protein is an important component of the mitosis and suppressor
gene. It is claimed that nano-chitosan hybrid material in a present work is an emerging
therapeutic for lung cancer. Popa et al. reported a polymeric nano capsules are based on
synthetic polymers like poly (N-vinylpyrrolidone-alt-itaconic anhydride) and
biopolymers like chitosan [73]. In this study, the nanocapsule is loaded with 5fluorouraucil for study of drug diffusion in lung cancer treatment.
2.5 Colon Cancer
Colon cancers are generally found from small non-cancerous tumors which form on the
inner walls of the large intestine. Colon cancer is the second-most common cause of
cancer related death and third-most common death [74]. Colon cancer has emerged as a
major public health problem, accounting for more than 1.4 million new cases and over
half a million deaths worldwide each year [75]. The treatment of colon cancer includes
chemotherapy, radiotherapy, biological therapy and surgery. Among these methods,
chemotherapy is one of the most common methods. Now days, the combination of
nanostructured polymeric nanoparticles (NP) and chemotherapy those can be broadly
13
applied in cancer treatment due to the controlled drug release properties in to the tumor,
and reduced adverse systematic effects associated with these formulations [76-78]. But
nanoparticles based approaches are seriously hindered by their low delivery
effectiveness, which prevents accumulation of sufficient therapeutic drugs in the tumor
cell for a sufficiently long period of time. The physicochemical characteristics of
nanoparticles (NPs) are generally depends upon Particle size, surface size, composition
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and surface hydrophilicity etc. [79-80]. Generally cellular uptake of NPs are depends
upon the high intracellular drug concentrations. Out of these physicochemical
characteristics, surface charge is an important factor that exerts the greatest influence on
drug delivery function [81]. But cationic NPs drag to negatively charged groups on the
cell surface to give facilitating cellular uptake and intracellular drug release [80]. That is
why, chitosan nanoparticles can be used in biomedical applications. These treatments
have serious side effects which may develop the death of the patient even after treatment.
Hence it is necessary to design less toxic biomaterials to fight against colon cancer.
Chitosan is a nontoxic biomaterial with less immune character and natural biodegradable
polymer. When a nanomaterial is incorporated in chitosan the stability, resistance and
strength of chitosan increases for which it becomes a good drugs carrier for colon cancer
treatment. At acidic conditions chitosan-functionalized NP is becomes positively charged
in tumors due to electrostatic interactions between negatively charged tumor cell
adsorption and tissue retention [82]. Venkatesan et al. developed that Hydroxyapatitechitosan nanocomposite can be an effective and safe vehicles for celecoxib delivery in
colon cancer chemotherapy [83].
14
2.6 Pancreatic Cancer
Pancreatic cancers are mostly found from malignant cells formed in the tissue of the
pancreas. Mainly it is caused by damage of the DNA. It is deadly form of neoplasm with
the highest level of humanity among cancers. 5-fluorouracil, gemcitabine and nucleotide
analogues are generally chemotherapeutic agents for pancreatic cancer treatment [84].
But this drug has been unsuccessful due to poor uptake in the cancer cells and the patients
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have a median survival of only 6.8 months [84]. One of the main advantages of chitosan
nanoparticles is its rapid uptake by cells due to its surface amine groups [85]. Pancreatic
cancer is one of the most common forms of cancer and the survival rate of this disease is
very low. Most of the pancreatic cancer patient would die within the first year of
diagnosis but only 5 % patients surviving beyond 5 years [84]. So developments of new
therapeutic strategies for the treatment of this disease are required. That is why Photo
dynamic therapies (PDT) are the development of new therapeutic disease is introduced as
treatments for cancer due to its fundamental specificity, selectivity, low lesion and
administration of a nontoxic drug [86]. PDT is recently reported as a viable treatment
option for pancreatic cancer [87-90]. This treatment has Sevier side effects which may
develop the death of the patient after treatment. So it is necessary to design less toxic
biomaterials to fight against pancreatic cancer. Chitosan is a nontoxic biomaterial with
less immune character, natural biodegradable polymer and mucoadhesive feature due to
their positive charge and negatively charged epithelia in small intestine, so increasing the
drug concentration of the site of absorption. Furthermore chitosan is the junction
between neighboring epithelial cells and par cellular transport of drug molecules leading
to enhance bioavailability of the drugs [91]. Cisplatin is an anti-cancer drug which is
15
decorated with the micro and nano voids of Nanostructured chitosan composites. The
negative basic site of the chitosan based biomaterials interacts with the positive cell of the
tumor affected by pancreatic cancer to inhibit the growth of tumor. Chitosan based
biomaterials and cisplatin drugs loaded for therapeutic application in pancreatic cancer is
schematically illustrated as Scheme 4. Nanostructured chitosan composites can act on
tumor cells directly to interfere with cell metabolism, inhibit cell growth. It also has an
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antitumor role through improving the body’s immune function to protect from pancreatic
cancer.
2.7 Metastatic Cancer
Metastatic diseases are generally found from colorectal cancer (CRC). Out of cancer
death, 70% CRC-related deaths are found in worldwide [92]. The treatment of metastatic
cancer includes biological therapy, combination chemotherapy and surgical resection.
Immunological escape of CRC cells and immune surveillance system of the liver are the
combinations of colorectal cancer liver metastasis [93-94]. It has been developed that, the
growth of metastatic CRC cells is controlled over the host immune system and
exploitation of liver-resident [95-96]. These treatments have serious side effect, which
may develop the death of the patient after treatment. So it is necessary to design less toxic
biomaterials to fight against Metastatic cancer. Amongst non-viral vectors, chitosan is an
appropriate candidate for macromolecular delivery [97-98]. When a nanomaterial is
incorporated in chitosan the stability, resistance, and strength of chitosan increases for
which it becomes a good drugs carrier for metastatic cancer treatment. Nanostructured
chitosan loaded drugs for metastatic cancer therapy are represented in Scheme 5. In this
16
scheme, it is assumed that, the laser can penetrate soft tissues and can effectively induce
the ablation of primary tumor or lymph metastasis in the superficial tissues. Upon laser
irradiation, the drugs (5-Fluorouracil) loaded green chitosan nanocomposites (GC) can
directly kill the cancer cells in the primary tumor sites and lymphatic node with inhibiting
their further metastasis. Here role of stable nanostructured chitosan composites may act
as the heat shock protein (HSP) antigen in cancer treatment. The cytotoxic mechanism of
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CD8 T cells explains the elimination of infected cells of metastatic cancer affected part,
without the destruction of healthy tissue [99]. Further, Positive charges of nanostructured
chitosan composites have selective adsorption and neutralizing effects on the metastatic
cancer affected tumor cell surface. As a drug vehicle, it has a targeting function to liver,
spleen and lung.
2.8
Prostate Cancer
Prostate cancers are generally found in prostate gland in the male reproductive system. It
affects only men and it is the second most leading cause of cancer. It has no sign or
symptoms at an early stage but in the advanced stage, it shows so many signs of
decreasing force in the steam of urine, blood in the semen, trouble urinating, Discomfort
in the pelvic area and bone pain. The treatment of prostate cancer includes chemotherapy,
radiation therapy, hormonal therapy, and surgery. Bicalutamide is an antineoplastic
hormonal agent which is available in the market in tablet form and this tablet can be used
as a primary treatment of prostate cancer. But it has so many drawbacks like high
variability in pharmacokinetics after oral administration and low bioavailability due to
poor solubility. Hence there is required to develop a dose form that disables the
17
drawbacks and makes the target specific so that the side effects are also avoided [100102]. Nanoparticles are broadly used as target specific drug delivery systems [103-105].
PLGA is a one type of polymeric nanoparticles which has so many advantages like
biocompatibility, easy hydrolysis, and biodegradability. It is found that it is easily
removed from the body by the normal metabolic pathway. But PLGA has many
disadvantages. So avoid to the disadvantage, the surface modification of PLGA
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nanoparticle is required. Hence chitosan is generally used for surface modification as
degradation of PLGA. Chitosan is mainly used to control burst release of drugs. It can be
also used to increase the tumor adhesion and permeability of the carrier to the tumor site
[106-108]. Target specific drug delivery can be used to reduce the side effects of cancer
chemotherapy. These treatments have Sevier side effects which may develop the death of
the patient after treatment. Hence it is necessary to design less toxic biomaterials to fight
against prostate cancer. So chitosan is a nontoxic biomaterial with less immune character
and natural biodegradable polymer. The nanostructured chitosan composites loaded with
Doxazosin drugs for treatment of prostate cancer is schematically illustrated as Scheme 6.
When a nanomaterial is decorated in chitosan, the stability and resistance chitosan are
increased for which it becomes a good candidate to hold drugs for delivery in treatment
of prostate cancer.
CONCLUSION
The drug delivery is an increasingly promising strategy to overcome drawbacks and
complications connected with the classical chemotherapy approach for cancer treatment.
Nanostructured chitosan is a potent inhibitor of endothelial cell causing cancer, assists in
18
improvement in bone fracture healing, inhibits secondary breast and prostate tumor
establishment, and causes a decrease in fetal body size. Collectively, present review
indicates the chitosan nanocomposite is promising biomaterials for bone healing and
bone tumor control of a cancer affected patient. A strategic design of the nano carrier
material, coupled with cancer cell target selectivity, which can certainly raise the safety
and efficiency of anticancer materials. Further, stable nanostructured chitosan composite
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and drug have the characteristic mucoadhesive properties and they follow to the
gastrointestinal tract for a long time. Thus chitosan nanocomposites have the ability to
increase retention time and capable to release drugs for a long time to enable to make
them ideal drugs delivery vehicle. Recently, nanostructured chitosan composites have
acquired a significant advantage over their conventional types, due to high aspect ratio,
which gives them additional properties for biomedical applications. Further, the study on
the drug delivery behavior of nanostructured chitosan composites may lead to the
realization of more effective vehicles in drug delivery systems. The therapeutic
applications of nanostructured hybrid chitosan in drug delivery may explore a topic of
interest in a treatment of various cancers.
ACKNOWLEDGEMENT
Authors express their thanks to Department of Science and Technology, Government of
India for awarding Inspired Fellowship to Kalyani Prusty to pursue doctoral degree.
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Table 1. Different method of cancer treatment with various drugs encapsulated with
nanostructured hybrid chitosan by different methods
Cancer
Drugs
Method of drugs
References
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delivery
Melanoma Camptothecin
In vitro
Liu et al. (2010) [21]
Melanoma Epigallocatechin-3-gallate
In vitro and in vivo
Siddiqui et al. (2014) [22]
Bladder
β- Cyclodextrin
In vitro
Kottaschade et al. (2011) [23]
Breast
Doxorubicin
In vitro and in vivo
Yang et al. (2016) [24]
Breast
Doxorubicin
In vivo
Deng et al. (2014) [25]
Lung
Mesenchymal stem cells
In vitro and in vivo
Han et al. (2016) [26]
Colon
Interleukin-12
In vitro
Xu et al. (2012) [27]
Colon
Celecoxib
In vitro
Venkatesam et al. (2011) [28]
Colon
Camptothecin
In vitro
Xiao et al. (2015) [29]
Pancreatic
Quercetin and 5-Fluorouracil
In vitro
David et al. (2015) [30]
Pancreatic
Gemcitabine
In vitro
Meng et al. (2015) [31]
Pancreatic
Metformin
In vitro
Snima et al. (2012) [32]
Metastatic
Platinum (IV)
In vivo
Wang et al. (2014) [33]
Prostate
Doxazosin
In vitro
Batty et al. (2016) [34]
Prostate
Bicalutamide
In vitro
Dhas et al. (2015) [35]
29
Table 2. Chitosan composites with reinforcement of various nanostructured materials and
encapsulation of different drugs for cancer therapy.
Reinforcing nanostructured
Encapsulated Drugs
Reference
Graphene oxide
Camptothecin
Bao et al. (2011) [36]
Graphene oxide
Oligodeoxynucleotides
Zhang et al. (2017) [37]
Silica nanospheres
Cytotoxin
Deng et al. (2011) [38]
Layer double Hydroxide
Pirenoxine
Xu et al. (2016) [39]
Nano glycol
Camptothecin
Min et al. (2008) [9]
Iron Oxide
Doxorubicin
Badry et al. (2017) [40]
Iron oxide
Methotraxate
Lin et al. (2015) [41]
Copper sulphide
Penicillin-
Guo et al. (2014) [42]
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materials
streptomycin
Silver/MWCNT
Fluorouracil
Nivethaa et al. (2016) [43]
Calcium phosphate
Trypsin
Xie et al. (2014) [44]
Gold nano rod
Paclitaxel
Zhang et al. (2016) [45]
Nano copper sulfide
Ofloxacin
Pathania et al. (2016) [46]
Graphene Oxide
Doxorubicin
Lei et al. (2016) [47]
30
Downloaded by [University of Florida] at 23:04 25 October 2017
Scheme 1. Molecular structures of chitin and chitosan
31
Downloaded by [University of Florida] at 23:04 25 October 2017
Scheme 2. Therapeutic applications of nanostructured hybrid chitosan
bionanocomposites.
32
Scheme 3. Schematic representation of chitosan loaded drugs for melanoma cancer
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therapy
33
Scheme 4. Schematic representation of chitosan loaded drugs for pancreatic cancer
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therapy
34
Scheme 5. Schematic representation of nanostructured chitosan composites loaded drugs
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for metastatic cancer therapy
35
Scheme 6. Schematic representation of nanostructured chitosan composites loaded drugs
Downloaded by [University of Florida] at 23:04 25 October 2017
for treatment of prostate cancer.
36
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