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Woodhead Publishing Series in
Biomaterials
EMERGING APPLICATIONS
OF CARBON NANOTUBES IN
DRUG AND GENE DELIVERY
Edited by
PRASHANT KESHARWANI
Assistant Professor, Department of Pharmaceutics,
School of Pharmaceutical Education and Research,
Jamia Hamdard, New Delhi, India
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Contributors
Mohammad A.S. Abourehab

Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah,
Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, College of
Pharmacy, Minia University, Minia, Egypt
Mustafa A. Alheety
Department of Nursing, Al-Hadi University College, Baghdad, Iraq
Duygu Beduk
Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege
University, Bornova, Izmir, Turkey
Sanghamitra Chatterjee
Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai,
Maharashtra, India
Pavan Kumar Chintamaneni
Department of Pharmaceutics, GITAM School of Pharmacy, GITAM-Hyderabad
Campus, Hyderabad, Telangana, India
Rambabu Dandela
Department of Industrial and Engineering Chemistry, Institute of Chemical Technology
Mumbai-Indian Oil Odisha Campus, Bhubaneswar, Odisha, India
Mahdieh Darroudi
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science,
Mashhad, Iran
Ceren Durmus
Lopamudra Giri
Israel González-Méndez
Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México,
Circuito Exterior Ciudad Universitaria, México City, Mexico
Kenguva Gowtham
Simge Balaban Hanoglu
ix
x Contributors
Duygu Harmanci
Central Research Test and Analysis Laboratory Application and Research Center, Ege
Gowtham Kenguva
Prashant Kesharwani
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia
Hamdard, New Delhi, Delhi, India; University Institute of Pharma Sciences, Chandigarh
University, Mohali, Punjab, India
Renat R. Khaydrov
Institute of Nuclear Physics, Uzbekistan Academy of Sciences, Tashkent, Uzbekistan
Majid Khazaei
Mashhad, Iran; Metabolic Syndrome Research Centre, Mashhad University of Medical
Science, Mashhad, Iran
Praveen T. Krishnamurthy
Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher
Education & Research), Ooty, Tamil Nadu, India
G. Kusuma Kumari
Javier Lara-Romero
Facultad de Ingeniería Química, Universidad Michoacana de San Nicolás de Hidalgo,
Morelia, Michoacán, México
Ahmed R. Mahmood
Department of Medical Laboratory Technology, Imam Ja’afar Al-Sadiq University,
Kirkuk, Iraq
Abdulwahhab H. Majeed
Department of Chemistry, College of Science, Diyala University, Diyala, Iraq
Leqaa A. Mohammed
Department of Chemistry, College of Science, Diyala University, Diyala, Iraq
Seyedeh Elnaz Nazari
Mashhad, Iran
Ammu V.V. V. Ravi Kiran
Majid Rezayi
Medical Toxicology Research Centre, Mashhad University of Medical Science, Mashhad,
Iran; Metabolic Syndrome Research Centre, Mashhad University of Medical Science,
Contributors xi
Mashhad, Iran; Department of Medical Biotechnology and Nanotechnology, School of

Science, Mashhad University of Medical Science, Mashhad, Iran
Ernesto Rivera
Circuito Exterior Ciudad Universitaria, México City, México
Smruti Rekha Rout
Andrea Ruiu
Circuito Exterior Ciudad Universitaria, México City, México
Amirhossein Sahebkar
Applied Biomedical Research Center, Mashhad University of Medical Science, Mashhad,
Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad
University of Medical Sciences, Mashhad, Iran; Department of Biotechnology, School of
Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Kendra Sorroza-Martínez
Circuito Exterior Ciudad Universitaria, México City, Mexico
Suna Timur
Central Research Test and Analysis Laboratory Application and Research Center, Ege
University, Bornova, Izmir, Turkey; Department of Biotechnology, Graduate School of
Natural and Applied Sciences, Ege University, Bornova, Izmir, Turkey; Department of
Biochemistry, Faculty of Science, Ege University, Bornova, Izmir, Turkey
CHAPTER 1
Background of carbon nanotubes

for drug delivery systems
Mahdieh Darroudi1, Seyedeh Elnaz Nazari1, Prashant Kesharwani2,
Majid Rezayi3, 4, 5, Majid Khazaei1, 4 and Amirhossein Sahebkar6, 7, 8
1
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad,
Iran; 2Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard,
New Delhi, Delhi, India; 3Medical Toxicology Research Centre, Mashhad University of Medical
Science, Mashhad, Iran; 4Metabolic Syndrome Research Centre, Mashhad University of Medical Science,
Mashhad, Iran; 5Department of Medical Biotechnology and Nanotechnology, School of Science,
Mashhad University of Medical Science, Mashhad, Iran; 6Applied Biomedical Research Center, Mashhad
University of Medical Science, Mashhad, Iran; 7Biotechnology Research Center, Pharmaceutical
Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 8Department of
Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
1.1 Introduction
Biotechnology researchers have developed a keen interest toward nano-
technology and have been focusing on working with nanomaterials in
recent decades [1,2]. Because of their unique properties, nanomaterials are
particularly well-suited for biomedical applications. They are facile to
synthesize, can be modified in size, contain tunable surface chemistry,
provide large surface-to-volume ratios, and are generally biocompatible [3].
All of these features make nanomaterials promising for almost all aspects of
biotechnology, overcoming the many shortcomings in existing conven-
tional materials [4]. Following a pioneering study by Higuchi et al. on
albumin nanoparticles, it was suggested that nanomedicine could be an
effective tool to target tumors and cancer cells as the ability to avoid im-
mune system clearance is enhanced [5]. Nanoparticles have shown to have
positive results against coronary artery disease, and cancer cells, by effec-
tively avoiding clearance from immune system clearance [6e9]. Nano-
particles can be used to deliver a large variety of pharmaceuticals in a way
that is safer (through targeted nanomedicines by limiting the amount of
drug delivered) and more effective [10]. Biological and medical nano-
materials have been used for years, including liposomes [11], carbon
nanoparticles [12e17], dendrimers [18], ceramic nanoparticles [19], iron
oxide nanoparticles [20], titanium dioxide nanoparticles [21], magnetic
nanoparticles, polymer nanocomposites [18], silica and metal nanoparticles
[22]. Additionally, many different types of nanomaterials have been
Emerging Applications of Carbon Nanotubes in Drug and Gene Delivery
ISBN 978-0-323-85199-2 © 2023 Elsevier Ltd.
https://doi.org/10.1016/B978-0-323-85199-2.00009-1 All rights reserved. 1
2 Emerging Applications of Carbon Nanotubes in Drug and Gene Delivery
proposed as means of drug/gene delivery that respond to external stimuli.

In addition, drugs release from within these nanocarriers are triggered by
changes in pH, redox potential, enzyme activation, thermal gradients,
magnetic fields, light, and ultrasound [23].
Among the nanomaterials, carbon nanotubes (CNTs) have drawn
tremendous interest in the biomedical field because of both their promising
properties, including high drug loading capacity [24], high stability [25],
needle-like structure, high surface area [25], biocompatibility [26], flexible
interaction with cargo, considerable strength, outstanding mechanical and
electrical properties [27], and the ability to deliver drugs to specific tissues
[28]. Despite the advantages, it also has some disadvantages related to
toxicity and low biodegradability [29,30]. Although CNTs exhibit some
undesirable properties, they are still being utilized in medicine in innovative
ways, such as in drug delivery systems, gene delivery, gene therapy, diag-
nostic applications, as well as biosensors and vaccine delivery [29]. CNTs
have a variety of appealing properties in biomedical applications, as shown
in Table 1.1.
Though CNTs have several desirable biological properties, their
biosafety is often an issue of concern, particularly in regards to their use and
their biomedical applications. Therefore, a comprehensive assessment of the
in vivo impact of CNTs is required before wide-scale commercial
biomedical applications are undertaken. Studies on CNTs have been crit-
icized for their inaccuracies and incompleteness, ranging from animal
models that aren’t representative of human exposure routes to studies that
lack even a thorough description of the impurities, chemistry, charge, and
dimensions of the studied CNTs [37]. Graphene sheets are rolled seamlessly
as a cylindrical tube to form single-wall carbon nanotubes (SWCNT), as
well as multi-walled carbon nanotubes (MWCNTs), which are composed
of layers of graphene sheets stacked on one another. Moreover, there are
three main methods for the manufacture of CNTs: chemical vapor depo-
sition (CVD), laser ablation, and arc discharge [38]. In the current chapter
book, we summarize promising and not-so-promising studies showing the
importance of CNTs in a variety of biomedical applications. Many research
studies, particularly performed in year 2016e2022, are assessed with critical
insight into what these studies conclude. Herein, the uptake of CNTs, the
delivery of pharmaceutical agents using CNTs has been covered. We also
discuss concerns raised about the toxicology of CNTs at the end of this
study and outline what and where the field urgently needs to grow.
Background of carbon nanotubes for drug delivery systems 3
Table 1.1 Various applications of carbon nanotubes.

Application Description References
Diagnosing application
Bioimaging Carbon nanotube’s optical, electronic and [31,32]

and biosensing mechanical properties make it a promising
material for the production of
electrochemical and optical biosensors and
some other applications deriving from
CNTs because of their high photostability
and lack of quenching
Therapeutical application
Photothermal CNTs would produce heat by converting [33]
therapy near-infrared radiation (NIR).
Drug delivery The unique needle-like shape of carbon [34]
nanotubes with the ability to quickly
penetrate cell membranes makes them ideal
carriers of drugs/genes due to their high
surface area, multifunctional surface
chemistry, lack of immunogenicity, and high
surface area.
Tissue Carbon nanotubes can be used in tissue [35]
engineering engineering because of their
biocompatibility, stiffness, mimicking of
natural tissue nanofibers, cell adhesion and
proliferation stimulation, and ability to form
3D structures.
Lab-on-chip- Miniaturized systems such as lab-on-a-chip [36]
devices devices are used to examine drugs, grow
cells, and model diseases using tiny volumes
of fluid flowing in various channels. The
CNTs would be used in LOC devices as
membrane channels, sensors, and channels
walls.
1.2 Quantitative approaches

A significant application of nanoparticles is the delivery of drugs; because of
their large surface areas, nanoparticles are capable of delivering large quantities
of drugs or other medical cargos [39,40]. Therefore, developing efficient drug
delivery systems is vital to human health [41]. Theranostic with nanotech-
nology for cancer has emerged as a promising field that could integrate the
treatment and diagnosis of cancer by combining nanotechnologies with

therapeutic agents to enable targeted drug accumulation in cancer-specific
cells without affecting normal cells [42]. Drug delivery procedures should
be significantly improved to ensure sustainability, low disruptions, and precise
and accurate controlled delivery of drugs [43]. Nanomaterial-based drug
delivery systems have recently been studied, and a number of breakthroughs
have been noted thereafter. There have been numerous studies on drug
delivery systems in recent years [44,45]. The bibliometric is insufficient to
assess a research area outputs; it should include other inputs such as literature
reviews to discover the insight of publications trends [46]. This research aims
to explore the research status done in this field of study from past to the current
year by a bibliometric approach and qualitative literature review. To ensure
the reliability of the analysis and input data for the software, scientometric
studies utilizing recognized database such as Google Scholar, ISI Web of
Science, and Scopus have been accessed. This study used the Scopus database
for its extensive coverage and comprehensive content.
From 1965 to 2021, bibliometric searches were conducted in Google
Scholar, Scopus, PubMed, and Web of Science Core Collections
(n ¼ 70,300). Data were obtained from the online version of the core
collection in Web of Science on January 15, 2022 [47]. The “Carbon
nanotube*” OR “CNT*” OR “SWCNT*” OR “MWCNT*” to identify
all articles related to treatment from 1990 to 2022 that contain the keyword
in the title list, and 189,358 publications were encountered. Also, articles
using the keyword “Drug Delivery*” AND “Carbon nanotube*” OR
“CNT*” OR “SWCNT*” OR “MWCNT*” to identify all articles from
1990 to 2022 that contain the keyword in the title which, 4748 publica-
tions met the selection criteria. Upon further screening, only 3137 publi-
cations were categorized through “Drug Delivery*” AND “Carbon
Nanotube*” OR “CNT*” OR “MWCNT*” OR “SWCNT*” key-
words that were utilized for further analysis. Moreover, more data for this
study based on title search were derived from SCOPUS, and the time span
was from 1985 to 7rd February 7, 2022. Also, bibliometric studies were
carried out on the Google Scholar and PubMed databases, resulting in
70,300 publications and 1353 publications. This data collection with an
initial title search “Drug Delivery*” in the “Title of Article” has been done
on another well-known database Scopus [47]. There were almost 38,996
documents with the title of “Drug Delivery*”; and nearly 125,277 docu-
ments with the title of “Carbon Nanotube*” while the “CNT*” OR
“MWCNT*” title search terms were used to retrieve the data. The search
returned 3571 documents from SCOPUS database. After careful inspec-

tion, a total of 1846 publications were identified as suitable for subsequent
analysis from SCOPUS database. The search returned 1230 review papers,
201 letters, and 149 conference papers (Fig. 1.1). Besides, Index Keywords
capture an article’s content with greater depth and variety [46].
The total number of records is 1846, and the total number of articles is
1332 in the sample period from 2012 to 2022. There are 160 author
contributions in 160 journals and 10 sub-divisions in the publications. 4637
words were identified as frequently used in this literature, and 1457 in-
stitutions contributed their articles from 62 countries (Fig. 1.2).
In Fig. 1.2c (inset), documents are categorized according to type in a
detailed classification. The articles with 52% and 1441 records represent a
significant portion of the total. Review documents accounted for 36% of
the total records, with 993 records. Total documents numbered 1332 in 7
categories accounted, due to their credibility and acceptance in scientific
communities, articles are strongly preferred as the document type by the
authors.
Record identified throughout database including: Google Scholar 70300, Scupos 125277,
WOS 189358, PubMed 1353
searching n= 386288, 347292 Duplicates removed
38996 articles excluded on the basis of not including

anticancer, drug delivery, or magnetic nanoparticles
3571 Selected Full-text articles assessed for eligibility
1846 Articles
11 Review papers
201 Letters
149 Conference papers
1846 Records included in the Systematic Review
Figure 1.1 Prisma flow diagram.

(a) (b)
600 Conference
Paper
3%
500 Book
Chapter Article
6%
400 Review
Book Chapter
300 Article Conference
Review 52% Paper
200 36% Editorial
Conference
100 Review
(c)
Figure 1.2 (a) The network of keywords, (b) clustering of keywords, and (c) categories
of the subject area, and inset categories by article type.
Keywords are highly influential on the mechanism and effectiveness of

document searches. Keywords serve as critical links among the range of
available documents to be identified as information sources. In Fig. 1.2a, the
top two keywords are carbon nanotubes and drug delivery, with 459 and
337 occurrences, respectively. In order to identify the document imme-
diately and in a timely manner, it is obvious that the exact link words or
phrases should be used. Based on the screening of the 25 top keywords, we
found that the most popular keywords fall into two categories: the com-
pound name and the application of the compound. Another effective
keyword with more than 50 occurrences is carbon nanotube, walled
carbon, single-walled, multi-walled, molecular dynamic, delivery system,

multi-walled carbon, drug release, wall carbon, and cancer therapy. These
keywords will be helpful in identifying the document that best describes
carbon nanotubes and their applications for future researchers. Fig. 1.3
displays the occurrences of the keywords.
To understand the different phases of growth of the publication
numbers, the collected data was organized chronologically. Fig. 1.3 depicts
(a)
16%
14%
12%
10%
8%
6%
4%
2%
0%
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
(b)
Figure 1.3 (a) Trend topic growth between 2012 and 2022, and (b) average article
published per year time span 2012e22.
the schematic representation of yearly increases in record numbers.

Research on carbon nanotube and drug delivery shows a slow onset with
few publications between 2012 and 2016. The trend was downward from
2016 to 2017. As exhibited in the trend topic growth, an increase was
depicted in 2017 based on both keywords carbon nanotube, and drug
delivery system, which there is a good consolidation with publication
trends. By 2022, there will be an increasing trend in publications. The
records showed growth between 2017 and 2020 from 9% to 14%. There
were 135, 164, and 178 records published in 2019, 2020, and 2021,
respectively, and a percentage of 10%, 12%, and 14% was recorded. New
developments and application in drug delivery and carbon nanotubes
related materials explains the increase in publications since 2017.
Fig. 1.4 presents a ranking of the countries involved in carbon nano-
tubes research according to the number of documents they have produced.
India, the United States, and China produce the most documents, with
576, 518, and 514. China had 6257 citations, while the United States had
3419. It is noteworthy that the China achieved a higher ratio of citations to
documents than USA. Iran is ranked 4th overall, followed by the United
Kingdom in 4th place, Italy in 6th place, and South Korea in 7th place.
There has been a noticeable increase in research in Carbon nanotube usage
in the drug delivery system as shown by the reported achievements. The
majority of the contributions originate from China, India, and the United
States. Several country collaboration clusters show the importance of group
research contributions and the current trends. Chart 4C depicting various
clustering patterns of Cluster 1 identifies it as the most productive.
Furthermore, Fig. 1.4a presents a geographic map of the countries involved.
This graph is drawn by the VOSviewer package (www.vosviewer.com),
which is a tool for comprehensive science mapping analysis for quantitative
research in bibliometrics [48,49]. Also, the red color intensity states the four
highest number of related documents published in each country. From the
data in the graph, Fig. 1.4a exhibited that between 50 countries, India,
China, and the United States have specialized studies earlier than other
countries with the most significant number of normalized strong collabo-
ration links to other countries with the rate of 20% of publication. China,
the United States, and Iran have the rate of 18.6%, 18.5%, and 12%,
respectively, after India in the mentioned topic. A three-field plot (Sankey
Diagram) listing the respective institute, authors, and keywords on the
considered topic is shown in Fig. 1.4c. This figure shows the relationship
among top institutes, top authors, and top authors’ keywords. The top five
Figure 1.4 Publication of carbon nanotube in drug delivery system research papers:
top countries and clusters (a and b), and (c) three-field plot of top-author, top-
countries; and top authors’ keywords on the considered topic.
institutes in which these documents were published included “Ministry of

Education China” (58 DOC), “Islamic Azad University” (53 Docs),
“Chinese Academy of Sciences” (42 Docs), “CNRS center national de la
Researche Scientifique” (35 Doc), and “Tehran University of Medical
Sciences” (31 Docs). The top five authors also include Jain, N. K, Mehra,
N. K., Kostarelos, K., Raissi, H., and Bianco, H., based on drug delivery
and carbon nanotube keywords.
Figure 1.4 Cont'd
1.3 CNT morphology and structure

The cylindrical sheet of graphene with carbon atoms bonded as sp2 hy-
bridization is thought to resemble hollow fullerene tubes. The carbon
nanotubes are composed of carbon sheets made from rolled graphite, which
is a source of carbon allotropes as well as graphite and fullerenes [50]. In
many fields, carbon nanotubes are used in the form of buckytubes, with
their cylindrical shape and unique properties. In addition to their me-
chanical, thermal, optical, and electrical properties, they also possess the
following characteristics [51]. High stiffness and robustness abound in
nanotubes, which also permit reversible collapse and buckling. In hexagonal
networks, the high axial Young’s modulus (degree of stiffness) results in
tensile strengths of 150 GPa due to the high CeC bond rigidity [52]. CNTs
are thus among the most rigid materials known while still being able to
buckle (elastic deformation) when subjected to compression forces [53]. In
addition to the rudimentary constituents, carbon assemblies form many
different configurations and shapes [54]. Under high pressure, nanotubes
can be assimilated, resulting in a strong, infinite-length wire by replacing
several sp2 bonds with sp3. The uncovered CNTs were discovered in recent
years by Irjima, who described multi-walled CNTs in carbon soot pro-
duced by the development of the C60 molecule in an arc evaporation
method for the first time [54].
1.4 Classification of CNTs

Nanotubes may indeed be alienated into various classifications based upon
the number of sheets of graphene existent in the CNTs. The following are
therefore sub-divided into:
1.4.1 Single-walled CNTs (SWCNTs)

Single-walled CNTs are formed by orienting a graphene sheet on a single
wall. A catalyst is required for the synthesis of SWCNTs, resulting in a non-
pure CNT without complexity with a readily twisted structure [55].
Sometimes, they appear as fluffy black powder or granular flakes with a
metallic appearance [56]. A variety of SWCNTs are available, which can be
trundled up as a seamless tube in multiple ways. When organized according
to their chirality and diameter, SWCNTs may act more like clearly
delineated semiconducting, metallic, or semi-metallic structures [57]. There
is a new technique published in US patients for preparing arrays or tightly
packed bundles of single-walled CNTs, with a diameter of less than 0.2m
that would be helpful in meeting commercially feasible reaction re-
quirements [51].
1.4.2 Multi-walled CNTs (MWCNTs)

These are the CNTs that contain multilayered graphene rolled over
themselves have varying diameters ranging from 2 to 50 nm which in turn
depends on the number of tubes [58]. Its synthesis is catalyst-free, and the
MWCTs are highly complex and cannot be twisted easily [51]. These tubes
have a distance of approximately 0.34 nm in between layers [59]. Their
typical form appears in form of fluffy black and granular powders. There are
MWCNTs of two different types based on the graphitic sheet arrangement
pattern. As an example of this, we can look at the Russian-doll model
where the graphitic sheets form concentrically aligned sheets, for example, a
length of (0, 14) SWCNT surrounding a shorter length (0, 12) SWCNT.
Graphite is rolled around itself in the second model, resembling a scroll of
parchment or a rolled-up newspaper [60].
1.4.3 Double-walled carbon nanotubes (DWCNTs)

There is another type of CNT that is similar to SWCNTs which also has
two concentric layers that enclose both the inner and outer tubes of these
nanotubes. These nanotubes are of serious concern in the pharmaceutical
industry [55].
1.4.4 CNT types based on chirality

Chirality is a crucial factor in determining the electrical properties of CNTs.
Depending on the chirality, CNTs can be categorized as an armchair,
zigzag, and chiral, as illustrated in Fig. 1.5 [60]. In the armchair, an
arrangement of bonds in one of the chairs is perpendicular to the tube axis;
in zigzag, there is an arrangement of bonds in which the tube has a V shape
perpendicular to the tube axis. Chiral or helical configuration are both
contrary to the above two types [57,61]. Conductivity and electrical
characteristics of CNTs are both effective indicators of CNT chirality and
may be used as a basis for nanoelectronic devices [62,63]. Based on their
structural transformations, preparation technique, and solubility character-
istics, CNTs are categorized into specific contexts, such as functionalized,
surfactant-assisted, solvent dispersed, and biomolecular assisted nanotubes
[64].
Armchair
Zigzag
(a) Armchair (b) Chiral
(c) SWCNTs (d) MWCNTs

Figure 1.5 Type of carbon nanotubes.
1.5 Drug loading on carbon nanotubes

The term “drug loading” refers to the combination of drug and carrier,
which delivers the active medication to the target cells or tissues. CNTs are
widely used for this purpose, particularly for large-scale drug delivery
because of their high surface-to-volume ratio and sphere-shaped shape [65].
Moreover, amphiphilic or hydrophilic polymers on CNT surfaces can in-
crease their loading capacity [66,67]. In addition to this, the chemical
functionalization of nanotubes’ surfaces could also enhance CNTs’
biocompatibility [68,69]. Modification of CNTs can be achieved through
the covalent attachment of PEG layers on their surface, PAMAM den-
drimers on their surface, amphiphilic deblock copolymers on their surface,
or dispersing the modified materials in a matrix of hyaluronic acid. The
mechanical strength of CNTs, like SWCNTs, enhances the properties of
both polymeric and non-polymeric composites [70]. It is also noteworthy
that these nanomaterials can also carry pharmaceutical agents by encapsu-
lating them within hollow cavities [71], adsorbing them within the walls of
CNTs, and binding them to their surfaces upon functionalization [72]. A
drug delivery system involving encapsulation has more advantages because
the drugs are released in a specific way within the targeted cells while
preventing their degradation [73]. Table 1.2 shows how therapeutic drugs
Table 1.2 Mechanism of loading drug.

Type of carbon Process of
Entry Drug nanotube immobilization References
1 Pregabalin SWCNT Encapsulation [74]
2 Doxorubicin Armchair and Adsorption [75]
zigzag CNT
3 Ifosfamide Armchair Encapsulation [76]
SWCNT
4 Paclitaxel f-MWCNT Encapsulation [77]
5 Doxorubicin Covalent-f- Adsorption and [78]
MWCNT encapsulating of drug
6 Cisplatin Carboxyl-f- Encapsulation [79]
MWCNTs
7 Doxorubicin MWCNT-FA Encapsulation [80]
8 Ciprofloxacin PEG/Gel- Grafting in [81]
Chit- nanocomposite matrix
MWCNT
9 Doxorubicin f-SWCNT Encapsulation [82]
would be attached to different types of carbon nanotubes. Various chemical

and electrical methods are available for controlling the release of drugs from
CNTs. CNTs can also be sealed with polypyrrole (PPy) film in order to
prevent drug release [83]. Drug delivery systems could be made more se-
lective by using homing devices, such as epidermal growth factor (EGF), or
folic acid [84]. A wide range of biomedical applications may be possible for
CNTs as a drug delivery carriers.
Unlike encapsulation or “endohedral modification” [73], these CNTs
serve to maintain the structural integrity of drugs, which helps to minimize
their degradation and in turn maximize their release from within them
under controlled conditions [85]. Due to hydrophobic and capillary forces,
this approach is most useful for drugs with low surface tension. For instance,
Fig. 1.6 shows how nanoparticles of gold are incorporated into the carbon
nano bottles to prevent the uncontrolled release of the encapsulated drug
(cisplatin) [86]. When the drugs are loaded by exohedral modification (as
opposed to encapsulation), it becomes much more exposed. Tethering
refers to covalent interactions with noncovalently attached drugs; as one of
the bio-conjugation methods. A further step of oxidation is required in the
tethering process before functional groups can be produced for conjugation.
Additionally, a covalent bond may change the drug’s molecular structure,
thereby altering its bioactivity and specificity [87]. This tethering approach
is superior due to strong covalent bonds that produce a stable platform
Figure 1.6 Schematic illustration of cisplatin delivery system and possible internali-
zation method of carbon nanotube including loading of the drug on the surface of
carbon nanotube, then cisplatin carried inside, in vivo study of current nanocarrier and
pH-responsive releasing drug leading to decreasing of tumor size.
between nanocarriers and drugs rather than the non-covalent method,

which ultimately causes the undesirable dissociation of therapeutic agents in
biological fluids. CNTs are generally used to deliver drugs to target cells in
the following way. Modified CNTs contain chemical receptors that attach
to drug molecules. Drug molecules are transported by these chemical re-
ceptors inside nanotubes [88]. Depending on the method used, the received
conjugate can be injected into the body through injection, oral adminis-
tration, or directly upon contact with the targeted cell. Using the endo-
cytosis pathway, the drug-loaded into CNT capsules can be internalized by
the chemical receptors and eventually emitted by the cells [88]. Fig. 1.6 is a
schematic illustration of an effective drug delivery system.
1.5.1 CNTs and cellular uptake

It is crucial to understand how drugs are taken up by the projected cells to
comprehend drug pharmacokinetics and pharmacodynamics. There must be
a better understanding of biochemical pathways and drug permeation across
cellular membranes. Drugs with high solubility are thought to be absorbed
primarily through diffusion through the lipid bilayer. However, in the case of
high molecular weight drugs, such mechanism is impaired, as low lip-
ophilicity interferes in passing through the bilayer structure [89]. CNTs have
remarkable properties that allow them to be absorbed by a wide variety of
cells. CNTs can penetrate cell membranes efficiently because of their needle-
like shape, which can be either good or bad depending on the intended
application. Hence, CNTs are suitable for a range of biomedical applications,
including the delivery of therapeutic agents and genes [90]. Although many
studies have been conducted on cellular uptake, there are still many questions
regarding cellular pathways initiated by CNTs and the delivery of therapeutic
agents and genes [91]. Furthermore, not only is it essential to determine how
cells take up CNTs, but if the CNTs will deliver drugs viably to the cells.
Therefore, it is extremely important to carefully study CNT internalization.
Several (not one) pathways, depending on the properties of the CNTs, have
been elucidated for cellular uptake of CNTs [92]. Some comprehensive re-
views show that there is no single mechanism for cellular uptake of CNTs.
In particular, CNTs can be internalized via various mechanisms, including
(1) direct penetration through the cell membrane or (2) passive and active
uptake, which have also been called independent and dependent pathways,
accordingly [93]. Below is a summary of the current literature on CNT entry
into various cells, emphasizing dimensions, cell types, and CNT faces (Fig. 1.7).
Figure 1.7 Cellular uptake of carbon nanotube into endocytic vesicles.
The distribution of CNTs within cells can occur either passively

through diffusion across the cell membrane lipid bilayer or through needle
mechanisms. CNTs overcome such barriers due to their needle-like
structure and high respect ratios [27]. CNTs can also be internalized by
endocytosis, which can be classified into five groups: phagocytoses, pino-
cytosis, caveolin-mediated endocytosis, clathrin/clathrin-mediated endo-
cytosis, and clathrin/caveolae independent. A phagocytic pathway is the
process in which large particles (w1 mm) enter cells. It predominantly
occurs within neutrophils, macrophages, and monocytes. Cellular uptake
occurs primarily through receptor-mediated endocytosis, which involves
clathrin-coated endocytic vacuoles. Caveolae gets invaded by nanomaterials
60 nm in diameter, which contains high levels of cholesterol and sphin-
golipids. The Caveolin-mediated endocytosis process is responsible for
transporting vesicular material and entrapping viruses and bacteria. Caveolin
and clathrin are known to play a role in cellular endocytosis and can
facilitate the internalization of CNTs with a diameter of 100 nm.
The macropinocytosis mechanism is thought to take up CNTs that are larger
than 300 nm. While the entry of CNTs and their drug cargo may offer many
advantages, each mechanism also has drawbacks that should be considered. There
are several features that influence cellular uptakes, such as CNT types (MWCNTs
or SWCNTs), dimension, surface charge, surface functionalization, degree of
aggregation, functional group chemistry, cell type, and agglomeration [94].
1.5.2 Size of CNTs

The previous studies demonstrated that CNTs with a smaller diameter
result in a higher cellular uptake [22,95]. A number of mechanisms are
involved in the passage of short CNTs through cell membranes, but active
endocytosis, particularly clathrin-mediated endocytosis, is generally the
most important [96,97]. Indeed, the shorter the CNT, the greater the
chance of passive internalization. In this regard, Zhang et al. evaluated cell
uptake based on CNT particle size and compared CNT particle sizes of
eight types, consisting of MWCNTs and SWCNTs, with macrophages
(RAW264.7), ranging in sizes from 30 to 400 nm. Their results indicated
that macrophages were able to take up CNTs in more significant quan-
tities when their particle size increased after increasing cytotoxicity, with
energy-dependent phagocytosis as the primary mechanism of cellular
uptake [98].
1.5.3 Degree of agglomeration and aggregation

The degree of agglomeration and aggregation of CNTs may affect their
internalization. A study by Song et al. found that higher concentrations of
O-MWCNTs resulted in higher uptake within human epithelial cervical
cancer cells (HeLa). However, these cells were not cytotoxic at concen-
trations of less than 150 mg/mL [99]. The amount of agglomeration and
toxicity increased slightly when the concentration of O-MWCNTs was
raised to 150 mg/mL. According to their findings, agglomeration assisted
endocytosis of O-MWCNTs occurred due to their ability to interact
effectively with cells. A regulated agglomeration of CNTs in some delivery
systems is capable of facilitating the delivery of drugs/genes through their
high uptake and low toxicity. A study conducted by Kuroda et al.
demonstrated that aggregated CNTs enhances uptake in RAW264 cells
[100]. This suggests that aggregation would be effective on uptake
mechanisms.
1.5.4 Surface charge

CNTs can be modified for their surface charge by altering the electrostatic
interactions and dispersibility. Consequently, the surface charge would be
relevant to the uptake of NTs by cells, as well as other biological processes
[101]. The SWCNTs were functionalized by Budhathoki-Uprety et al.
using polycarbodiimide polymers with carboxylic acids (COOH-CNT) or
primary amines (NH2-CNT) attached to their side chains, which these
complexes have surface charges of approximately 66.8 and 52.8 mV,

respectively [102,103]. Cationic nanotubes could be more readily incor-
porated into HeLa cells than anionic nanotubes. However, serum proteins
in the culture media adsorb CNTs in the cell culture media and influence
cellular uptake of these CNTs. It is important to remember that the pro-
teins adsorb to the nanomaterials that cells recognize, not the nanomaterial
itself. That is referred to as the “protein corona effect” of nanomaterials, a
layer of proteins adsorbed to a nanomaterial when exposed to body fluids
[104]. CNTs can therefore be designed so that they can be taken up by
cells. Consequently, CNTs can be designed to deliver drugs efficiently
when their surface chemistry is taken into account. The reactivity of
nanomaterials’ surfaces with cellular membranes contributes to their
toxicity. It is the nonbiodegradability of CNTs that gives them their
toxicological properties. The binding of blood proteins influences biolog-
ical pathways of the CNTs, and cytotoxicity can therefore be decreased as a
result [105]. According to Ge et al., blood proteins bind to the surface of
SWCNTs, enabling changes to their cellular interactions. This ultimately
reduces their cytotoxicity in two different human cell lines, including
human umbilical vein endothelial and acute human monocyte leukemia
(THP-1) cells.
1.5.5 Cell type

Cellular uptake rates and mechanisms may vary by the cellular system [106].
The internalization of CNTs was evaluated in human lung cancer cells
A549, human lung cancer cells Calu-6, human breast cells MCF-7, and
mouse macrophages J774 by Summers et al. He in his work demonstrated
that the highest CNT uptake occurred in the J774 cell line [101]. After
exposure to CNTs for 24 h, A549 cells had a w40% lower uptake than
J774 (which showed the highest uptake). There was no significant differ-
ence between the MCF-7 and Calu-6 cells, but both types comprised of
about 30% J774 CNTs. Additionally, macrophages could take up SWCNTs
more efficiently than fibroblasts. Although macrophages preferentially
phagocytose particles with a diameter of over 500 nm, fibroblasts primarily
endocytose particles with a diameter of 200 nm and less [107]. In addition,
J774 cells can take up larger particles and also the aggregates of CNTs. By
aggregating CNTs within phagocytic cells, nanoparticles are retained
within them, which makes them ideal carriers for CNT transportation into
tumor cells.
CNTs and their cellular uptake have been analyzed using a wide range
of techniques, including atomic force microscopy, transmission electron
microscopy, dynamic light scattering, fluorescence microscopy, surface-
enhanced Raman scattering, and confocal Raman spectroscopy. The
characterization and visualization of cellular uptake of CNTs are based on
some characteristics of CNTs, such as optical characteristics [107e109]. The
evolution of nanotechnology began with improvements in microscopy, and
this here depicts is no lesser truth in terms of CNT cellular
internationalization.
1.6 Drug delivery using carbon nanotubes

In recent decades, biomedical researchers have focused significant attention
on using CNTs for various purposes due to their high electrical, physico-
chemical, and mechanical properties and the high aspect ratio of CNTs. In
addition, they have been used as nanocarriers for the delivery of several
plasmid DNAs [110], proteins [111], peptides [112], siRNAs [113], and API
[114].
1.6.1 Antineoplastic APIs

Worldwide, cancer ranks second behind cardiovascular diseases. Various
unwanted toxic effects have been observed in the surrounding healthy
tissues as a result of APIs therapy [115]. One of the most challenging aspects
of therapeutic research remains drug delivery to cancerous cells [116]. This
is because tumor cells express P-glycoprotein (P-gp), which will block the
entry of therapeutic agents into the tissue. Therefore, most of the tumor-
targeted antineoplastic agents are unexpectedly destroyed before they can
kill the targeted cells. For the treatment of cancer, innovative technologies
are needed for delivering therapeutic agents [117].
Different nanomaterials have previously been utilized as drug delivery
agents. A wide variety of antineoplastic agents can be loaded in CNTs,
including doxorubicin, cisplatin, methotrexate, and camptothecin. As an
example, cisplatin has been used to treat a variety of cancer-related disor-
ders. Cisplatin stimulates cellular death by inhibiting DNA replication and
cross-linking between DNA strands. Despite its anticancer effect, this drug
produces many side effects, including ototoxic, nephrotoxic, and neuro-
toxic effects.
The chloride ions in plasma can obliterate the therapeutic effect of drugs
by causing an interference in their interaction with water. Due to this,
CNTs are used as drug carriers to reduce side effects by preventing the
deactivation of therapeutic agents. In one study, the synthesis of func-
tionalized SWCNTs containing cisplatin to target prostate cancer cell lines
PC3 and DU145 was reported. Cisplatin acts by penetrating deep within
the cellular membrane and selectively accumulating within the cytoplasm of
cancerous prostate cells based on findings of cellular uptake studies.
Therefore, the encapsulation of cisplatin has proved to be very effective
factor in stabilizing its administration to cancerous prostate cells [118].
It has also been extensively used for treating cancer with doxorubicin
drug as an anticancer therapeutic agent. The chemical structure of doxo-
rubicin has been shown in (Fig. 1.4b). The non-covalent complexation of
MWCNTs and functionalized SWCNTs with polyethylene glycol (PEG)
was also demonstrated by Hwang [119]. In an investigation, it was found
that MWCNTs combined with doxorubicin work better against cancerous
cells than doxorubicin alone. SWCNTs have been synthesized and modi-
fied with different types of polysaccharides as well as with doxorubicin and
folic acid in recent years [120]. In some cases, the release of therapeutic
agents from within these nanocarriers was reported to be pH dependent. In
this regard, CNTs are functionalized on the surface to control the rate of
drug release and loading efficiency. According to Fabbro et al. research
[116], a novel method is essential for improving the construction and
characterization of modified CNTs to allow them to be applied
therapeutically.
1.6.2 Anti-inflammatory APIs

Many studies have been conducted in order to enhance cellular uptake
properties over the years. In addition to improving the molecule release
profile, this also helps in reducing side effects [121]. Meanwhile, researchers
have also been looking at CNTs as a means of delivering anti-inflammatory
APIs. Zanella et al. (2007) investigated an anti-inflammatory drug known as
nimesulide on both Si-doped capped and pristine SWCNTs using first-
principal calculations (DFT). Based on DFT calculations, they reported
the use of CNTs as potential carriers for aromatic residues and have also
demonstrated improved physisorption with Si-doped SWCNTs due to
their electronic properties [122].
Due to the inefficiency of conventional administration strategies, anti-
inflammatory delivery systems provide stable plasma levels of the thera-
peutic agent over a longer period of time, allowing for extended drug
release profile. Additionally, osmotic pressure from the membrane sur-

rounding the therapeutic agent causes the drug to be absorbed from the
carrier. In one investigation, Madaenia et al. increased the hydrophilicity of
MWCNT by adding cellulose acetate, which resulted in increased indo-
methacin release from the membrane [123].
One alternative drug release technique called “stimulated drug release”
involves releasing therapeutic agents from a vehicle in response to various
stimuli, such as temperature, pH, and other physiological conditions.
Increasingly complex and intelligent systems can also be derived from
electrical signals and through microsystems [124]. Electrical signals have
stimulated dexamethasone release via SWCNTs-chitosan hydrogel films
developed by Arti Vashist and colleagues. In this paper, the authors
investigated whether electrostatic interactions would encompass indo-
methacin on functionalized SWCNTs. The CNTs are fully reversible once
the charge is activated, and as a result, indomethacin is released due to
electrostatic repulsion. Accordingly, SWCNTs can produce electrical sig-
nals that can control the release of therapeutic agents, improving the
bioavailability of active molecules [125].
1.6.3 Cardiovascular APIs

Cardiovascular diseases are heart and blood vessel disorders that cause death
in a large number of people worldwide [91]. In recent years, conventional
medicine has become the preferred method of treating cardiovascular dis-
ease. However, in the treatment of atherosclerosis and other cardiovascular
disorders, the use of anti-cardiovascular medications is confined by their
failure to cross the endothelium layers effectively. Using rosiglitazone, for
example, to treat atheroma through macrophage infiltration into athero-
sclerotic wounds, the drug acts as an agonist of the peroxisome proliferator-
activated receptor. The mechanism of action of this therapeutic agent may
be viewed through its toxicity to normal healthy cardiovascular tissues,
which can then result in the development of undesirable side effects such as
fluid retention (fluid retention) and heart failure [93,94].
Another delivery system is the macromolecular and thiomersal [126] and
utilization of silica particles within the delivery system [96] to deliver anti
cardiovascular drugs. In cardiology, nanoparticles based on silica are used to
deliver annexin V, which is crucial for achieving nanomaterials [127]. One
study described how CNTs have progressed impacts on treating cardio-
vascular disease [128]. Additionally, Liu et al. investigated the feasibility of
interactions between SWCNTs and nifedipine in order to further under-

stand: (1) interaction between CNTs and nifedipine, (2) absorption of the
therapeutic agent by the CNTs, and (3) the process of energy translocation.
It is mainly used to treat angina pectoris, hypertension, and other cardio-
vascular disorders by antagonizing calcium channels. CNTs spontaneously
encapsulate and adsorb nifedipine via van der Waals interactions by their
internal cavity [129].
However, modified nanotubes are better at encapsulating therapeutic
agents than pristine MWCNTs due to their hydrophilic nature [130]. The
researchers used pristine and oxidized CNTs in the same study to investi-
gate the loading mechanism of the therapeutic agent carvedilol. This drug
works principally as an adrenoceptor/vasodilator antagonist for treating
hypertension but may be beneficial to protecting the heart and nervous
system as well. For the loading of carvedilol into the internal cavity of
CNTs, the mentioned study used three different approaches, namely a
solvent method, a wetness impregnation method, and a fusion method.
Each approach contributes to the differences in loading capacity and car-
vedilol’s physical state.
1.6.4 Anti-infective APIs

The emergence of strong microorganisms that are resistant to many broad-
spectrum antibiotics makes it even more challenging to treat infectious
diseases in this modern age. In contrast, APIs that are used to treat infection
tend to have poor physisorption by the cells because of their poor solubility
and penetration [131]. Antibiotics remain a crucial part of modern medi-
cine. Even so, the invention of new therapeutic agents is a long and costly
process involving long-term laboratory studies and clinical trials. Conse-
quently, currently available carbon-based nanomaterials like CNTs are used
to deliver therapeutic agents in infected areas, that can in turn help over-
come bacterial resistance, and enhance drug solubility [132,133]. Ampho-
tericin B is a common agent used for treating fungal infections that is less
soluble in water. It is not recommended to administer this drug parenterally
because the chances of aggregation in the bloodstream is high. This issue has
been addressed through several strategies, including formulation of
amphotericin B with MWCNT: to increase its cellular uptake, enhance its
therapeutic effect against different pathogens, enhance its dispersion in
water, and reduce aggregation in the bloodstream after administering
parenterally [134]. In addition to Candida albicans, Candida parapsilosis
ATCC 90118, and Cryptococcus neoformans ATCC 90112, conjugation
of Amphotericin B and MWCNT has been reported to have significant

antifungal effects. Furthermore, API modified with MWCNTs showed no
toxicity to mammalian cells when absorbed rapidly by cell membranes.
MWCNTs can protect therapeutic agents, such as dapsone, from being
metabolized by antibacterial agents. Thus, in the liver, the cytotoxicity is
substantially reduced due to an increase in anti-mycobacterial activity [133].
1.6.5 Gene therapy

A new technology, gene therapy, was developed in the 1980s that allowed
cells to deliver nucleic acids to treat genetic defects. Viruses and non-viral
genetic systems require reliable and robust delivery systems to transport
nucleic acid into their targeted cells. The transport of genes within the cell
is also studied extensively with nanomaterials, such as carbon nanotubes,
polymeric nanoparticles, and liposomes. Their immunogenicity, nucleic
acid diameters, and suitability for scale-up processes make them excellent
choices for nanoarchitecture [135]. It is generally recognized that cationic
polyelectrolytes like dendrimers, protamine sulfate, and polylysine offer us
an option for developing non-viral mechanisms of DNA delivery [136].
These systems enhance the ability of the cell to absorb DNA by endocytosis
and safely transport it to the nucleus following non-covalent binding with
the nucleic acid. There are several polycationic functionalized carbon
nanotubes that have demonstrated the capacity to transport human DNA
plasmids using polycationic carbon nanotubes. The findings demonstrate
the transport of plasmid DNA around carbon nanotubes and the success of
the therapeutic system to increase gene expression in marker genes. These
studies confirm the feasibility and effectiveness of this approach [137].
1.6.6 The delivery system using conjugated CNT-liposomes

As an excellent vehicle for therapeutic agent delivery, CNTs are exten-
sively explored due to their ease of transport by cellular membranes. CNTs
bind to the covalent structure of liposomes and form conjugates with them
[138]. Covalently attached liposomes are a reliable method for delivering
therapeutic agents across cellular membranes. CNT can be loaded with a
wide range of drugs which can be used to treat specific targets due to the
cavity inside each CNT. CNTs modified in this way have opened up new
possibilities in biological investigation. Various functionalized-CNT devices
are reported to have demonstrated stable biological applications, including
better cellular uptake of drugs and nucleic acid delivery [117,139,140].
Another random document with
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was a veritable citadel in course of construction, with armoured
trenches, sandbag emplacements for big guns, barbed-wire
entanglements; in fact, everything that modern military science can
contrive to insure impregnability.
The whole place was teeming with activity, and looked like a
gigantic ant-heap; on all sides soldiers were to be seen at work, and
it was evident that those in charge of this important position were
determined to leave nothing to luck. The little that nature had left
unprotected was being made good by the untiring efforts and genius
of the Italians, and the Austrian chances of ever capturing the place
are practically nil. Its curious configuration largely contributes to its
impregnability and power of resistance if ever besieged.
Behind its line of armoured trenches is a deep hollow, which could
shelter an army corps if necessary; and here, under complete cover,
are well-built, barrack-like buildings, in which the troops can be
comfortably quartered during the long winter months when the fort is
buried under yards of snow and practically isolated from the outer
world.
As he whirled past in the big car (see page 50)
To face page 88
The position on the Forcola is probably unique in the world, as it is

situated exactly at a point where three frontiers meet: the Italian,
Austrian and Swiss. From its sandbag ramparts on the front facing
the Austrians one has the most sublime vista of mountain scenery it
would be possible to conceive. It is impossible in mere words to
attempt to convey anything but the faintest impression of it, yet it
would be a sin of omission not to endeavour to.
As I gazed in front of me, the marvellous beauty of the scene held
me in rapt suspense, and for a few moments the war passed from
my mind.
The Austrian Tyrol was before me, a panorama of wondrous
mountain peaks stretching away into the mist of the far distance, and
towering above the highest was the mighty Ortler, crowned with
eternal snow, and positively awe-inspiring in its stately grandeur.
My reverie was abruptly disturbed by the boom of a big gun. I was
back again amongst realities, yet how puny did the biggest efforts of
mankind at war appear in comparison with all this splendour of
nature. Had it not been for the echoes produced by these giant
peaks the report of even the heavy artillery would probably have
scarcely been heard.
The Swiss and Austrian frontiers meet on the summit of a
Brobdingnagian cliff of rock of strange formation, which towers
above the Forcola. Through field glasses the frontier guards and the
blockhouses are plainly discernable.
This overhanging proximity of the enemy strikes me as constituting
a constant menace to the Italian position, as every movement within
its enceinte is visible from the height above. The fact also of the
Austrian and Swiss frontier guards being so close to each other as to
be able to fraternise must inevitably conduce to espionage.
Doubtless, however, all this has been well considered by the Italians,
and they are not likely to be caught napping.
Rateau and I had a very cordial reception, and the officer in
command of the position took a visible pride in showing us round it
and explaining everything, whilst I made a lot of interesting sketches.
The ability and rapidity with which it had been constructed and
fortified were worthy of the very highest praise. Such a fortress
brought into being in so short a time and at such an altitude was in
itself such a marvel of military capacity that one was lost in wonder
at it all. Evidently no obstacle presented by nature deterred its
accomplishment.
In the emplacements were guns of a calibre one certainly never
expected to see except in the valley, and you were lost in conjecture
how the feat of getting them up here was achieved.
Everything was approaching completion, and by the time the snow
set in and the position would be practically cut off from the lower
world it would be a big, self-contained arsenal with all that was
necessary for carrying on its share of the general scheme of
operations on the Frontier without extraneous assistance should the
rigours of the Alpine winter render it unapproachable.
In the warfare in the mountains, positions develop more or less
into isolated communities, as the men seldom have an opportunity of
going down to the busy world below, besides which the summer is so
brief at these altitudes. Even on the date we were at the Forcola, the
twentieth of August, there were already unmistakable signs of the
approach of winter; the air was decidedly frosty—there had been a
fall of snow a few hours previously, and most of the peaks were
powdered with silvery white.
We gladly accepted the invitation to have some lunch in the mess-
room, for the keen air had given both of us healthy appetites, and
while we were doing justice to a well-cooked steak with fried
potatoes and a flask of very excellent Valtellino. I had a chat with
some of the younger officers, and learned to my surprise that they
had not stirred from the place since they had come up nearly three
months before, and they had no hope of getting leave for a long time
to come as things were developing and the winter coming along. A
visit from two civilians like ourselves, who could give them some
news of the outside world, was therefore a veritable red-letter day for
them.
Yet, in spite of the monotony of their existence, these cheery
fellows did not complain. There was always plenty to occupy their
minds, they said, and prevent them from brooding over old times. To
defend the Forcola at all hazards was now their sole pre-occupation;
and after all, they added, with an attempt at mirth, they might easily
have been stationed in a still more isolated spot and with fewer
companions. Such admirable equanimity was only what I expected
to find now that I knew the Italian soldier, so it did not surprise me at
all.
After lunch, as the Austrian batteries seemed to be getting busier,
we strolled up to the “observation post,” a sort of tunnel in which was
a telephone installation and an instrument known as a “goniometre,”
a powerful telescope in miniature, combined with a novel kind of
range-finder, through which the slightest movement of the enemy
can be instantly detected and telephoned to the officers in command
of the different gun emplacements. The machine is always in
readiness, as it is so fixed that once it is focussed it requires no re-
adjustment.
There was a small, irregular hole at the end of the tunnel that
faced the enemy’s line, and through this the goniometre pointed.
Two soldiers were on duty, one to keep his eye on the opposite
mountain, the other to manipulate the telephone. It evidently required
some practice to use the telescope, as I had a good look through it
and could scarcely make out anything.
When we visited the post the Italian batteries were not yet replying
to what I was informed were only the usual daily greetings of the
Austrians, but their response would doubtless be sent in due course,
judging from the conversation of the operator with the telephone.
Everything we saw was so absorbingly interesting that we should
have liked to remain on the Forcola many hours more, but time was
getting on by now, and we had to think of getting back.
As may be imagined, after my experience coming up I was
particularly dreading this moment to arrive. I thought it best,
however, to say nothing and trust to luck in getting down without
another attack of vertigo. When we said goodbye to our genial hosts,
several soldiers were about to descend also, so we were to have
company.
“Three minutes interval between each man and go as fast as
possible,” called out an officer, and off went everyone at a given
signal. Rateau was just before me and, as it turned out, I was last.
I felt like the prisoners in the Conciergerie during the reign of terror
must have felt as they waited their turn to go out to the fatal tumbril.
Through the opening in the sandbags only a bit of the narrow
pathway was visible, as it turned sharply to the right and went down
the face of the cliff beyond. It was like looking out on limitless space.
“Well, goodbye and a pleasant journey,” said the officer to me
when my turn came.
Out I went, putting my hand over my left eye to avoid looking into
the void, and I managed to run like this all the way down.
It was getting late when we got back to Bormio, so we decided to
remain another night, and were glad we did, as an amusing incident
occurred during the evening.
Whilst we were finishing dinner at the hotel, we received a note
inviting us afterwards to smoke a cigar and take a glass of wine with
the sergeants of the regiment quartered in the town. Of course we
accepted and duly turned up.
The reception—for such it was—took place in a large private room
of the hotel we were staying in, and we were greeted with the utmost
cordiality.
There was a big display of a certain very famous brand of
champagne on a side table, and the corks soon began to fly merrily;
toasts were given as usual, and everything was pleasant. During a
pause a sergeant next to me, who spoke French fluently, asked me
how I liked the wine.
In jocular vein I replied that it was excellent, but it was a pity it is
German, as it is well known that the owner of the vineyards near
Rheims is at present interned in France. To my surprise he took my
words seriously; there was an icy moment as he communicated my
remarks to his comrades, and then, as though with one accord, there
was a crash of broken glass, and we had to finish up the evening for
patriotic reasons on Asti Spumante.
CHAPTER IX
From Brescia to Verona—Absence of military movement in rural

districts—Verona—No time for sightseeing—The axis of the Trentino
—Roveretto, the focus of operations—Fort Pozzachio—A “dummy
fortress”—Wasted labour—Interesting incident—Excursion to Ala—
Lunch to the correspondents—Ingenious ferry-boat on River Adige—
The Valley of the Adige—Wonderful panorama—“No sketching
allowed”—Curious finish of incident—Austrian positions—Desperate
fighting—From Verona to Vicenza—The positions of Fiera di
Primiero—Capture of Monte Marmolada—The Dolomites—Their
weird fascination—A striking incident—The attempted suicide—The
Col di Lana—Up the mountains on mules—Sturdy Alpini—Method of
getting guns and supplies to these great heights—The observation
post and telephone cabin on summit—The Colonel of Artillery—What
it would have cost to capture the Col di Lana then—The Colonel has
an idea—The idea put into execution—The development of the idea
—Effect on the Col di Lana—An object lesson—The Colonel gets
into hot water—The return down the mountains—Caprili—Under fire
—We make for shelter—The village muck-heap—Unpleasant
position—A fine example of coolness—The wounded mule—An
impromptu dressing.
CHAPTER IX
It has been said that “who holds the Trentino holds not merely the
line of the Alps and the Passes, but the mouths of the Passes and
the villages which debouch into the Lombard Plain.”
The significance of this statement was being continually brought
home to me here on this northern frontier of Italy, and you could not
shut your eyes to the fact that the very safety of the whole country
depended on the army making good its “tiger spring” in the first
hours of the war.
It was not so much the necessity for an aggressive movement, but
for what one might term a successful defensive—offensive, and it
cannot be gainsaid—and even the Austrians themselves would
admit it, that in this respect the Italians scored everywhere along the
line.
General Cadorna’s remarkable power of intuition was evidenced
by every movement of the army from the outset, but nowhere more
noticeably than in the Trentino sector at this early stage of the war,
when the slightest miscalculation on his part would most assuredly
have spelt irretrievable disaster for Italy.
We were to have abundant proof of what his organizing genius,
combined with the patriotic ardour of the troops, had been able to
accomplish in the short space of three months.
After eight days spent in and around Brescia we motored to
Verona, the next stage as arranged on our programme. Our road
was across country, and therefore some considerable distance from
the Front, so beyond being a delightful trip through glorious scenery,
there was nothing very special about it; touring motorists having
done it hundreds of times.
There was a noteworthy absence of any signs of military
movements in the rural districts, and the peasants were apparently
going about their usual peaceful avocations as unconcernedly as
though the war were in another country instead of being a
comparatively short distance away. In this respect, however, one felt
that the motor journeys we were scheduled to make from centre to
centre would prove exceedingly interesting, as they would afford us
an insight of the conditions prevailing in the rear of the Front, not an
unimportant factor in forming one’s impressions.
In Verona, had one been holiday making, many hours might have
been profitably spent in “doing” the place. As it was, my time was
fully occupied from the hour we arrived till the moment we left, and it
was, I am grieved to have to confess it, only by accident that I was
able to snatch the time to see anything of the artistic treasures of the
famous old city.
As a matter of fact, you scarcely had a moment to yourself if you
wanted to get any work done, as we only remained three days in
Verona.
The reason for thus curtailing our stay did not transpire. In this
sector of the Front the most important operations in the Trentino
were taking place, and the Austrians were straining every nerve in
order to stay the victorious progress of the Italians, but the lightning
rapidity of their advance had proved irresistible, and had forced a
retirement to their second line. To dislodge them from this was the
tack the Italians had before them when we were in Verona.
The axis of the Trentino is obviously Trent, and in due course of
time it will doubtless fall into the hands of the Italians, but the date of
that event is on the knees of the gods.
Meanwhile the focus of the operations in August 1915, was the
fortified position of Roveretto, which has been described as the
“strategic heart” of the Trentino, and which guards the Austrian
portion of the valley of the Adige. Enclosed within several rings of
entrenchments and an outer chain of modern forts of the most
formidable character, it presented a redoubtable barrier to the
advance of the Italians into the Trentino in this direction.
But the lightning-like strategy of Cadorna upset all the plans of the
Austrian generals and, formidable though these defences were, they
were gradually being mastered.
Fort Pozzachio, which might have proved the most serious
obstacle of all, and have involved a long siege before it was
captured, turned out to be little more than a dummy fortress in so far
as defensive possibilities were concerned, and had to be abandoned
at the commencement of the war. This step being decided on by the
Austrians in consequence, as they stated in their communiqué, of its
not being in readiness to offer any prolonged resistance if besieged.
It transpired later that, although years had been spent working on
it and vast sums of money expended, it was so far from being
completed when war was declared that its heavy armament had not
yet arrived. It had been intended to make of it a stronghold which
would be practically impregnable.
Even now, it is a veritable modern Ehrenbreitstein, but with this
difference: it is not built on a rock but excavated out of the summit of
a lofty craig, which is quite inaccessible from the Italian side.
Although only about four miles from Roveretto, its surrender did not
help the Italians over much, in so far as the operations in that zone
were immediately concerned, but its loss must have been a severe
blow to Austrian pride.
It was said that it had been the intention of the Austrians to blow it
up rather than let the Italians reap the advantage of all the labour
that they had wasted on it, and in this connection there was a story
going round at the time that seemed circumstantial enough to be
worth recounting.
On the day of the occupation of the fortress an engineer officer,
strolling about examining the construction of the place, happened to
catch his foot in what he took to be a loose telephone wire, which
had apparently been accidentally pulled in from outside.
In disengaging it his attention was attracted by a peculiar object
attached to the wire, when to his surprise he found that it was an
electrical contrivance connected with a live fuse leading to a positive
mine of dynamite in one of the lower galleries.
A small splinter of rock had somehow got mixed up with the
detonator, and thus, as though by a miracle, the fortress and the
Italian troops in it had been saved from destruction. Almost needless
to add, the wire led from the nearest Austrian position.
We only made one excursion from Verona, but it was of extreme
interest in view of what was taking place at the time in this sector of
the Front. It was to Ala, a small Austrian town in the valley of the
Adige, which had been captured a few weeks previously.
There had been some sharp fighting in the streets, as many of the
houses bore witness to, but its chief interest to us lay in the fact that
it was in redeemed territory, and actually within the portals of
Austrian Trentino. Like, however, most of the liberated towns I had
visited, Ala was more Italian than Austrian.
The whole region was positively alive with warlike energy
(see page 75)
To face page 100
The Mayor offered a lunch to the correspondents, and the usual

patriotic toasts followed. Afterwards we motored to the nearest
position, which was only a short distance from the town. Crossing
the river Adige on our way by an ingenious ferry-boat, constructed by
the engineers, the Austrians having destroyed the only bridge in the
vicinity. The “ferry” consisted of two big barges clamped together,
then boarded over and steered by an immense paddle projecting
from the after part. It was worked on the fixed-rope and sliding-pulley
principle, the swift current supplying the motive power.
We had all been looking forward to getting a good conception of
the operations, which just then were of vital importance, but we were
to be disappointed; we were only to be permitted a long range view.
On reaching a small hamlet on the bank of the river a few hundred
yards further on we were informed we could not proceed beyond this
point. We had, therefore, to be content with what we could see from
the roadway, which overlooked the river.
The coup d’oeil was magnificent, though not so impressive as
what we had seen previously. Before us stretched the broad valley of
the Adige; its swiftly running stream divided up here by numerous
gravel islets. On the opposite bank was the railway line to Trent and
the town of Seravalle; whilst facing it on our side was Chizzola.
Away in the distance bathed in the effulgence of the glorious
summer afternoon, were the Stivo and other high hills, on which are
the forts guarding Roveretto, hidden from our view by a bend in the
river.
Now and again one saw a tiny piff of white smoke, and heard the
muffled boom of artillery, but this was the only indication that any
operations were in progress. It was all so vast and so swamped as it
were by the immensity of the landscape that it was difficult to grasp
what was taking place.
A few hundred yards further down the road where we were
standing was the picturesque village of Pilcante, almost hidden in
luxuriant foliage.
In the immediate foreground and standing out in discordant detail
was a barbed-wire entanglement barricading the road, and guarded
by a detachment of infantry; whilst immediately below the parapet
which skirted the pathway, a cottage and a small garden on a spot of
ground jutting into the river had been transformed into a sort of
miniature “position” with an armoured trench, disguised by small
trees stuck in the walls.
It occurred to me that all this would make an interesting sketch; as
a matter of fact, it was the only subject that had appealed to me that
day, so I got out my book, and had just finished it when I felt a touch
on my shoulder and someone whispered in my ear:
“Be careful, sketching is not allowed here.” I looked round—it was
one of the officers accompanying us.
“Not allowed?” I queried; “surely there must be some mistake.”
“Not at all,” he replied; “special instructions were issued by the
General that no sketches or photographs were to be made here.”
As this was the first time I had heard of any restrictions since we
had started on the tour, my surprise may be imagined, and the more
especially as nothing apparently could have been more innocent
than the subject I had chosen.
“Well, I’m sorry, but what you tell me comes too late as I have
already made a sketch,” said I, showing it to him. “What shall I do?”
The officer, a very good fellow, laughed and shrugged his
shoulders: “Put your book back in your pocket and don’t let anyone
see it; there are several staff officers about.”
The finish of the incident was equally curious. I worked up a
double page drawing from the sketch in question, and, of course,
submitted it to the censors. It aroused a good deal of comment, but it
was eventually “passed” on condition that I altered the title and took
out all the names of the towns, mountains, etc.; only the vaguest
suggestion as to where I had made it being permitted.
In spite of the fact that the Austrians had the geographical
advantage of position almost everywhere, and that their frontier was
comparatively so close to many important Italian cities, the intrepid
advance of the Italian troops upset all the calculations of the Austrian
generals, and, instead of advancing into Italian territory, they found
themselves forced to act on the defensive some distance to the rear
of their first line positions, and well inside their own frontier. But it
was no easy task for the Italians, and tested their valour and
endurance to the utmost.
The fighting in the ravines and on the sides of the mountains was
of the most desperate character, for in this warfare at close quarters
it is man to man, and individual courage tells more than it does down
on the plains.
Here, in the fastnesses of nature, every clump of trees or isolated
rocks are potential ambuscades. So it requires the utmost caution,
combined with almost reckless daring, to advance at any time.
The Austrians, though well provided with heavy artillery, were quite
unable to hold on to their positions. It was brute force pitted against
skill and enthusiastic courage, and brute force was worsted as it
generally is under such conditions.
Our two next “stages,” Vicenza and Belluno, brought us into the
very heart of the fighting on the line of the Italian advance in the
Eastern Trentino towards Bolzano and the region round Monte
Cristallo.
We halted a couple of days at Vicenza to enable us to visit the
positions of Fiera di Primero. The Italian lines here were some
distance inside Austrian territory, so we had a good opportunity of
judging for ourselves the difficulties that had to be overcome to have
advanced so far, as well as the preparations that had been made by
the Austrians for their proposed invasion of Italy.
Cunningly concealed trenches, barbed-wire entanglements and
gun emplacements commanded every approach, whilst protecting
the advance of troops. It seemed incredible that such well planned
works should have been abandoned.
But here as elsewhere the lightning strategy of Cadorna left the
Austrian commanders no option. Monte Marmolada, 11,000 ft. high,
and other mountains on which the Austrians had placed heavy
artillery, were captured by degrees. The strategic value of these
positions was incontestable.
Unless one has seen the Dolomites it is impossible to form any
conception of what these successes mean or the terrible difficulties
that had to be surmounted to gain them.
Neither Dante nor Doré in their wildest and most fantastic
compositions ever conceived anything more awe-inspiring than
warfare amidst these towering peaks.
At all times they exercise a kind of weird fascination which is
positively uncanny; add the thunder of modern artillery and the effect
is supernatural. You try hard to realize what it means fighting
amongst these jagged pinnacles and on the edges of the awful
precipices.
Death, however, has little terror for the men, judging from the look
on the faces of the mortally wounded one saw from time to time
brought down from the trenches.
A little incident related to me by Calza Bedolo brings home the
spirit of Italy’s soldiers.
He had shortly before come upon a stretcher-party carrying down
from the mountains a very dangerously wounded man. Upon enquiry
as to how the wound had been caused he was informed that it was a
case of attempted suicide.
What had led up to this desperate act? It appeared that for some
trivial breach of discipline the man had been deprived of the privilege
of a place in the front trenches and sent to a position in the rear!
The most important of all the strategic points at that time was the
Col di Lana, which dominates the Falzarego and Livinallongo
passes, close to Cortina d’Ampezzo. Here the Austrians were putting
up a defence which was taxing the strength and resources of the
Italians, to their utmost, but it was gradually being overcome.
Every mountain which commanded the position was being
mounted with guns of the heaviest calibre, and big events were said
to be looming in the near future.
As a matter of fact, it was only six months later that the Italians
succeeded in capturing the Col di Lana, so strongly were the
Austrians entrenched on it. A young engineer conceived the idea of
mining it, and so successful was he that the entire summit of the
mountain, with the Austrian positions, was literally blown away.
One of the most interesting of the excursions the English group of
correspondents made was to the top of a mountain facing it. As it
would have been a very trying climb for amateur mountaineers like
ourselves, mules were considerately supplied by the General of the
division. So we accomplished the ascent in easy fashion, for it was
certain that very few of us would have tackled it on foot.
The sturdy Alpini who accompanied us treated the excursion as a
good sort of joke apparently, and plodded steadily alongside us in
the test of spirits, laughing now and again at our vain efforts to keep
our steeds from walking on the extreme edge of the precipices.
This ride gave us a splendid opportunity of seeing how the Italians
have surmounted the difficulty of getting heavy artillery to the very
summits of mountains, where no human foot had trodden before the
war broke out. Rough and terribly steep in places though the road
was, still it was a real roadway and not a mere track as one might
have expected to find considering how rapidly it had been made.
Men were still at work consolidating it at the turns on scientific
principles, and in a few weeks, with the continual traffic passing up
and down it, it would present all the appearance of an old
established road.
It is the method of getting the guns and supplies up these great
heights in the first instance that “starts” the road as it were. Nothing
could be simpler or more efficacious.
It consists in actually cutting the track for the guns just in advance
of them as they are gradually pushed and hauled forward. The
position and angle of the track being settled before starting by the
engineers.
This, of course, takes time at first, especially when the acclivity is
very steep, but it has the advantage of breaking the way for
whatever follows. The rough track is then gradually improved upon
by the succeeding gun teams, and so a well constructed zig-zag
military roadway gradually comes into being.
We left the mules a short distance from the summit and had to
climb the rest of the way. Instead of an artillery position as we
expected to find, it was an observation post, with a telephone cabin
built in a gap in the rocks, and a hut for half a dozen soldiers on duty.
The little station was quite hidden from the Austrians, although
only a couple of thousand yards distant. It was a most important
spot, as from here the fire of all the batteries round about was
controlled.
We were received by the Colonel commanding this sector of the
artillery, a grizzled warrior, wearing a knitted woollen sleeping cap
pulled well down over his ears, which gave him a somewhat quaint
and unmilitary appearance.
The “observation post” was merely a small hole through the rocks,
and so awkward to get at that only two people could look through it
at the same time. Immediately facing you across a shallow valley
was a barren hill of no great elevation (of course it must be
remembered we were here several thousand feet up). There was no
sign of life or vegetation, and it looked so singularly bare and
uninteresting that unless you had been told to look at it your attention
would never have been attracted to it.
Yet this was the much talked of Col di Lana. Seen, however,
through field glasses its aspect altered considerably, and you could
not fail to notice what appeared to be row upon row of battered stone
walls, and also that the ridge was very much broken up, shewing
patches everywhere of red sand.
The “stone walls,” the Colonel told us, were what remained of the
Austrian trenches and the patches of sand were caused by the
incessant bombardment by the Italians. At that moment there was
not the slightest sign of military activity anywhere, no sound of a gun
disturbed the still air.
It seemed incredible that we were gazing on the most redoubtable
position on the whole Front, and one that for weeks had barred the
Italian advance in this direction.
Someone remarked that it did not look so very formidable after all,
and asked the Colonel if it would really mean a very big effort to
capture it.
“To take that innocent looking summit now,” he replied gravely,
“would necessitate attacking it with a couple of hundred thousand
men and being prepared to lose half of them. We shall get it by other
means, but it will take some time; meanwhile every yard of it is
covered by my batteries.”
We continued to gaze on the silent landscape with increasing
interest, when suddenly, as though an idea had occurred to him, the
Colonel said that if we did not mind waiting twenty minutes or so he
would show us what his gunners could do. Of course we asked for
nothing better. So he went up to the telephone cabin and was there a
little while; he then came back and told us to follow him.
He led the way down a ravine enclosed by lofty cliffs close by. At
the foot of it were large boulders, some with sandbags spread on
them. This was his sharpshooter’s lair, he informed us, but for the
moment they were not there.
We were then told to hide ourselves as much as possible behind
the rocks and watch what was going to happen on the Col di Lana,
which was in full view from here.
“We are right under fire here, but you are fairly safe if you keep
well under cover,” he added, as a sort of final recommendation when
he saw us all placed.
The stillness of death reigned for the next ten minutes perhaps.
We kept our eyes glued on the fateful hill opposite, not exactly
knowing what was going to happen, when all of a sudden there was
the crash of a big gun and we heard the shriek of a shell as it passed
overhead; then, with scarcely an interval this was followed up by
such a succession of firing that it sounded like a thunderstorm let
loose.
The effect on the Col di Lana was startling: it was as though a
series of volcanoes had started activity, all along the summit and just
below it fantastic columns of smoke and dust rose high into the air.
As the Colonel had truly said, every yard of the hill was under the fire
of his batteries.
It was an object lesson in precision of aim, and one almost felt
sorry for the men who were thus, without the slightest warning,
deluged with high explosives. Meanwhile the Austrian batteries did
not fire a shot in reply.
The bombardment lasted exactly ten minutes, and ceased as
abruptly as it had started.
“Wonderful,” we all exclaimed when we were reassembled at the
station. The Colonel looked delighted with the way his instructions
had been carried out.
At that moment we heard the telephone bell ringing violently; he
excused himself and hurried to the box, and was there some
minutes. When he returned the look of elation on his face had
disappeared.
“That was the General ringing up,” he explained. “He heard the
firing and wanted to know what had happened suddenly. He is in an
awful rage at my giving you this entertainment.”
Of course we were all very sorry that he should have got into
trouble on our account, but he seemed to make light of it, and
evidently had no fear of unpleasant consequences. We then left the
place and retraced our footsteps.
There was no mule-riding going down the mountain unless you
wanted to break your neck. It was far too steep, therefore we had to
walk the whole way, a very long and tiring job.
In the valley below was the village of Caprile, where we had
arranged to meet our cars. A mountain stream ran past the village,
and there was a broad, open space of ground facing the houses, in
which was a large encampment with long sheds and hundreds of
horses and mules picketted.
As we were walking across to the inn, where we were going to
lunch, we heard the dull boom of a gun in the distance, and in a few
seconds the approaching wail of a projectile, followed by the report
of the explosion a short distance away, and we saw the shell had
burst on the hillside a few feet from the Red Cross Hospital.

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Emerging Applications of Carbon Nanotubes in Drug and Gene Delivery Prashant Kesharwani Full Chapter

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Emerging Applications of Carbon

Nanotubes in Drug and Gene Delivery

Copyright © 2023 Elsevier Ltd. All rights reserved.

For information on all Woodhead Publishing publications visit our

Publisher: Matthew Deans

Mohammad A.S. Abourehab

Mashhad, Iran; Department of Medical Biotechnology and Nanotechnology, School of

Background of carbon nanotubes

proposed as means of drug/gene delivery that respond to external stimuli.

Table 1.1 Various applications of carbon nanotubes.

Bioimaging Carbon nanotube’s optical, electronic and [31,32]

1.2 Quantitative approaches

treatment and diagnosis of cancer by combining nanotechnologies with

returned 3571 documents from SCOPUS database. After careful inspec-

38996 articles excluded on the basis of not including

3571 Selected Full-text articles assessed for eligibility

1846 Records included in the Systematic Review

Figure 1.1 Prisma ﬂow diagram.

Keywords are highly inﬂuential on the mechanism and effectiveness of

carbon, single-walled, multi-walled, molecular dynamic, delivery system,

the schematic representation of yearly increases in record numbers.

institutes in which these documents were published included “Ministry of

Figure 1.4 Cont'd

1.3 CNT morphology and structure

1.4 Classiﬁcation of CNTs

1.4.1 Single-walled CNTs (SWCNTs)

1.4.2 Multi-walled CNTs (MWCNTs)

1.4.3 Double-walled carbon nanotubes (DWCNTs)

1.4.4 CNT types based on chirality

(a) Armchair (b) Chiral

(c) SWCNTs (d) MWCNTs

1.5 Drug loading on carbon nanotubes

Table 1.2 Mechanism of loading drug.

would be attached to different types of carbon nanotubes. Various chemical

between nanocarriers and drugs rather than the non-covalent method,

1.5.1 CNTs and cellular uptake

Figure 1.7 Cellular uptake of carbon nanotube into endocytic vesicles.

The distribution of CNTs within cells can occur either passively

1.5.2 Size of CNTs

1.5.3 Degree of agglomeration and aggregation

1.5.4 Surface charge

complexes have surface charges of approximately 66.8 and 52.8 mV,

1.5.5 Cell type

1.6 Drug delivery using carbon nanotubes

1.6.1 Antineoplastic APIs

1.6.2 Anti-inﬂammatory APIs

release proﬁle. Additionally, osmotic pressure from the membrane sur-

1.6.3 Cardiovascular APIs

interactions between SWCNTs and nifedipine in order to further under-

1.6.4 Anti-infective APIs

of Amphotericin B and MWCNT has been reported to have signiﬁcant

1.6.5 Gene therapy

1.6.6 The delivery system using conjugated CNT-liposomes

The position on the Forcola is probably unique in the world, as it is

From Brescia to Verona—Absence of military movement in rural

The Mayor offered a lunch to the correspondents, and the usual

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