This document discusses applications of carbon nanotubes for drug delivery systems. Carbon nanotubes have unique properties like high surface area and thermal conductivity that make them promising candidates for drug transport and delivery. They can be functionalized for biomedical applications through covalent and non-covalent methods. Carbon nanotubes show potential as drug carriers for cancer treatment, transdermal drug delivery, cardiac regulation, and tissue regeneration. Different synthesis techniques like arc discharge, laser ablation, and chemical vapor deposition are used to produce carbon nanotubes in large quantities.

1. APPLICATIONS OF CARBON NANOTUBES
FOR DRUG DELIVERY
SYSTEMS
PRESENTED BY :
MURTAZA PUTLIWALA
M.PHARM, SGSITS

2. INTRODUCTION
 Carbon nanotubes are cylindrical carbon molecules have
Novel properties.
 They can be about 1/50,000th the thickness of a human
hair.
 Their unique surface area, stiffness, strength and
resilience have led to much excitement in the field of
pharmacy.
 High Thermal conductivity.
 Excellent electron emission characterstics.
 Good candidates for a wide variety of applications,
including drug transporters, new therapeutics, delivery
systems and diagnostics.

3. STRUCTURE OF CARBON NANOTUBES
 Carbon nanotube (CNT ; also known as buckytubes) is an
allotrope of Carbon that is Graphite , in which Carbon atom
have sp2 hybridized state.
 Nanotubes are cylindrical fullerenes.
 CNT, which have been constructed with length-to-diameter
ratio of up to 132,000,000:1.
 Diameters of the carbon nanotubes have ranging from 2 nm to
55 nm. The lengths of CNT are typically several microns.
 Configurationally it is two
dimensional graphene (a single
sheet of graphite ) sheet rolled
up with continuous unbroken
hexagonal mesh into a
cylindrical tube.

4. GEOMETRY OF CARBON NANOTUBES
ARMCHAIR ARRANGEMENT ZIGZIG ARRANGEMENT
CHIRAL ARRANGEMENT

5. TYPES OF CARBON NANOTUBES
1. SINGLE WALLED NANOTUBES :
 The diameter of single-walled
nanotubes (SWNTs) has approximately
to 1 nanometer.
 SWNT are wrapping with layer of
graphite which one-atom-thick layer
called graphene into a seamless
cylinder.
 It requires catalyst for their synthesis.
 Less accumulation in the body.

6. CONTD…
2. MULTIPLE WALLED NANOTUBES :
 Multi-walled nano tubes (MWNT)
consist of multiple rolled layers
(concentric tubes) of graphite.
 It has very complex structure
 It can be produced without catalyst.
 Purity of product is high.
 More chances for accumulation in the
body.

7. Synthesis of Carbon Nanotube
Various Techniques have been developed to produce
nanotubes in sizeable quantities, which includs :
1. Arc discharge
2. Laser ablation
3. Chemical vapor deposition (CVD).

8. Arc Discharge Method
• It is the first macroscopic
production of carbon
nanotubes.
• Its cost very high and gives
yield up to 30 – 90 %
• During this process, the carbon
contained in the negative
electrode sublimates because
of the high discharge
temperatures.
• At 100 amps, carbon vaporizes
and forms hot plasma.

9. Chemical Vapor Deposition (CVD)
 The catalytic vapor phase deposition of carbon
was first reported in 1959 .
 Most economical method due to cheapest source
of material i.e Fossil hydrocarbon and gives yield
upto 20-100%
•During CVD, a substrate is prepared with a layer of
metal catalyst particles, most commonly nickel,
cobalt, iron, or a combination.
•The diameters of the nanotubes that are to be
grown are related to the size of the metal particles.
•Nanotubes grow at the sites of the metal catalyst;
the carbon-containing gas is broken apart at the
surface of the catalyst particle, and the carbon is
transported to the edges of the particle, where it
forms the nanotubes.

10. Laser Ablation Method
• In the laser ablation process, a pulsed laser vaporizes a graphite target
in a high-temperature reactor .
• A water-cooled surface may be included in the system to collect the
nanotubes.
• The laser ablation method yields
around 70% and produces
primarily single-walled carbon
nanotubes with a controllable
diameter determined by the
reaction temperature.
• it is more expensive than either
arc discharge or chemical vapor
deposition.

11. FUNCTIONALIZATION OF CARBON NANOTUBES FOR
BIOLOGICAL APPLICATIONS:
• Raw carbon nanotubes have highly hydrophobic
surfaces, and are not soluble in aqueous solutions.
• For biomedical applications, surface chemistry or
functionalization is required to solubilize CNTs
improve biocompatibility and low toxicity.
• Two type of Surface fuctionalization of carbon
nanotubes :
Covalent
Noncovalent
• Surface fuctionalization of carbon nanotubes

12. Covalent fuctionalization
• By attaching hydrophilic polymers such as poly ethylene glycol
(PEG) to oxidized CNTs, yielding CNT-polymer conjugates
stable in biological environments.
• Covalently PEGylated SWNTs synthesized by this strategy for
both In vitro and in vivo applications.
Non Covalent fuctionalization
• NCF of CNTs can be carried out by coating CNTs with amphiphilic
surfactant molecules or polymers.
• NCF of SWNTs by PEGylated phospholipids (PL-PEG) high water
solubility of nanotubes and versatile functionalities Phospholipids
are the major component of cell membranes, and are safe to use in
biological systems.

13. APPLICATIONS OF CNTs
A) Carbon Nanotube Membranes for Transdermal
Drug Delivery
B) CNT’S for cancer treatment
C) CNTs for Cardiac Autonomic Regulation
D) CNTs for platelet activation
E) CNT for tissue regeneration
F) Carbon Nanotubes in Drug Delivery: Future Trends

14. Carbon Nanotube Membranes for
Transdermal Drug Delivery
• Transdermal systems are attractive methods of drug administration
specifically when treating patients for drug addiction such as nicotine for
smoking cessation.
• Through the use of functionalized carbon nanotube (CNT) membranes,
drug delivery to the skin can be controlled by applying a small electrical
bias to create a programmable drug delivery system.
• a transdermal patch system that can be tailored to an individual’s needs
will increase patient compliance as well as provide much more effi cient
therapy.

15. CNT’S for cancer treatment
• CNT’s can be considered as antitumor agents and when in
combination with conventional drugs, can significantly enhance their
chemotherapeutic effect with the help of the advanced drug delivery
system.
• It has been reported that Paclitaxel loaded PEG-CNT’s are promising
for cancer therapeutics.
• There are three key features of this nanoscale drug delivery system
(DDS):
1. Use of functionalized SWCNTs as a biocompatible platform for
the delivery of therapeutic drugs or diagnostics.
2. Conjugation of prodrug modules of an anticancer agent that is
activated to its cytotoxic form inside the tumor cells upon
internalization and in situ drug release.
3. Attachment of tumor-recognition modules to the nanotube
surface (binding EGFR antibody)

16. Mechanism by which CNTs enter cells
• Incorporation of the drug Either by :
– Loading into hollow CNT
– Attaching at their outer surface
 Attachment of the anticancer drug to the outer surface of the CNT can
be through either covalent or noncovalent bonding.
 CNT with a diameter of 80 nm can be loaded up to 5 million drug
molecules.
These are :
 Passive diffusion of CNTs through the lipid bilayers of the cell membrane
 Attachment of CNTs to the external cell membrane, resulting in its absorption by the
cell using an energy-dependent process, such as Pinocytosis.
 Endocytosis : Engulfing of CNTs directly by cell.

17. Summary of Anticancer drug delivery via carbon nanotubes
CNT
Type of
cancer/disease In vivo/in vitro Drug Method of loading
SWCNTs Ovarian cancer NA Gemcitabine Use of external forces to particles in a
selected direction
SWCNTs Leukemia In vitro Daunorubicin Daunorubicin incubated in phosphate-
buffered saline at 37°C for 16 hours with
SWCNTs
SWCNTs Breast cancer In vitro and in
mice
Paclitaxel Paclitaxel was modified by succinic
anhydride, adding a carboxyl group at
the C-2-OH position SWCNTs with
branched PEG-NH2
MWCNTs Human gastric
carcinoma
In vitro and in
mice
HCPT(10-
hydroxycamptot
hecin)
HCPT is linked to MWCNTs using
diaminotriethylene glycol (hydrophilic
spacer) biocleavable ester linkage
SWCNTs Chorio- ,
nasopharyngeal
epidermoid
testicular
carcinoma
In vitro Platinum (IV) The SWCNT-PL-PEG-NH2 was initially
formed. The SWCNT coated with PEG
was then reacted with the platinum in
the presence of coupling agents
including EDC (1-ethyl-3-(3-
dimethylaminopropyl) carbodiimide
hydrochloride)and NHS

18. Summary of Anticancer drug delivery via carbon nanotubes
CNT
Type of
cancer/diseas
e In vivo/in vitro Drug Method of loading
SWCNTs52 Cervical
cancer
In vitro siRNA SWCNTs reacted with PL-PEG. For the
incorporation of disulfide bond, the amide group
of PEG was attached to a heterobifunctional
crosslinker (sulfo-LC-SPDP). The siRNA was then
attached to SWCNTs via a disulfide bond
SWCNTs43 Lymphoma In mice Doxorubicin SWCNTs were sonicated in a solution of PL-PEG
followed by centrifugation. Excess surfactant was
removed by filtration and washing. Doxorubicin
loading onto pegylated SWCNTs was carried out by
mixing.
MWCNs51 Breast cancer In vitro Methotrexate Amine-MWCNTs was generated through 1,3-
dipolar cycloaddition reaction of zomethineylides.
Methotrexate was reacted with f-MWCNTs
through coupling agents, ie, HATU and DIEA

19. CNTs for Cardiac Autonomic
Regulation
• There are single-walled carbon nanotubes used in the
cardiac autonomic regulation.
• Single-walled carbon nanotubes are portion of
physicochemical properties with fine component which
may damage cardiovascular autonomic control that
proved after the study in rats.
• SWCNTs may alter the baroreflex function, then affecting
the autonomic cardiovascular control regulation

20. CNTs for platelet activation
• SWCNTs using alongwith platelet P-selectin when injected into
anaesthetized mice, light dye induced thrombus formation
was found and the platelet found to be activated.
• Activate blood platelets by inducing extracellular Ca2+ influx
that could be inhibited by calcium channel blockers.

21. CNT for tissue regeneration
• CNTs are combined with polymers such as poly-l-lactide,
Polylactide and poly-D,Llactide- coglycolide copolymer which
have been used as a scaffolds in tissue regeneration.
• It can be prepared by mixing solubilized collagen with solution
having carboxylated SWCNTs.
• Living smooth muscle cell were integrated at the collagen
stage to produce cell-seeded collagen carbon nanotubes.

22. Carbon Nanotubes in Drug Delivery:
Recent Trends
• f-CNTs have been demonstrated to deliver proteins, nucleic acids, drugs,
antibodies and other therapeutics.
• Ammonium functionalized CNTs can also be considered very promising vectors for
gene-encoding nucleic acids.
• CNT’s in Gene Therapy : Gene therapy involves transport of the correct gene by
viral or nonviral vectors to the affected area
• CNTs seem to represent a very good nonviral vector for gene therapy, because they
can cross the cell membrane by an endocytosis process, and also, because of the
functionalization of CNTs, the DNA can be transferred without any degradation.
• The siRNA delivered via MWCNTs achieved significant inhibition of tumor growth.

23. Commercially available Carbon Nanotubes
• Specification details for carbon nanotubes (SWCT & MWCT)
available from Aldrich Materials Science, Sigma-Aldrich Co. LLC.
Aldrich Product No. TEM Image Description
755710 Single-walled isolated and bundled carbon
Nanotubes powder
2 nm x several µm (length, measured by
TEM / SEM) Carbon purity : > 70 % (by TGA)
Metal oxide impurity: < 30 % (by TGA) High
specific surface area (> 1000 m2/g )
755133
Thin multi-walled (avg. 7~9 walls) carbon
nanotubes powder 9.5 nm (diameter, by
TEM) x 1.5 µm (length, by TEM)
Carbon purity : > 95 % (by TGA)
Metal oxide impurity: < 5 % (by TGA)
High level of purity.

24. Aldrich Product No. TEM Image Description
755168 Double-walled isolated and
bundled carbon nanotubes powder
3.5 nm (diameter, by HRTEM) x 1 -
10 µm (length, by TEM / SEM)
Carbon purity : > 90 % (by TGA)
Metal oxide impurity: < 10 % (by
TGA) Specific surface
area: >500 m2/g (by BET)
High filed emission characteristics
Transparency
755141 Short double-walled isolated and
bundled carbon nanotubes powder
3.5 nm (diameter, by HRTEM) x 3
µm (length, by TEM / SEM)
Carbon purity : > 90 % (by TGA)
Metal oxide impurity: < 10 % (by
TGA) Surface chemistry
characteristics.
755125 Short thin multi-walled (avg. 7~9
walls) carbon nanotubes powder
9.5 nm (diameter, by TEM) x < 1 µm
(length, by TEM) Carbon purity : >
95 % (by TGA) Metal oxide
impurity: < 5 % (by TGA) Surface
chemistry characteristics Ease of
dispersability

25. Why only Carbon Nanotubes out of
tremendous Nanocarriers?
• CNTs act as promising drug carrier due to their unique chemical, physical,
and biological properties, nanoneedle shape, hollow monolithic structure,
and their ability to obtain the desired functional groups on their outer
layers.
• In case of gene therapy liposomes and microparticles, seem not to be a
safer option because of their poor pharmacokinetic profile of the
administered oligonucleotide and conjugated plasmid DNA.
• They can be functionalized to be more water-soluble and serum-stable,
with low toxicity at the cellular level.
• Detection CNTs does not require any type of fluorescent labelling, such as
quantum dots. It can be detected directly by TEM or AFM due to their
electron emission spectroscopy.
• Destruction of cancer cells for thermal ablation.
• Another application of CNTs for drug delivery is intravenous injection.

26. Thank You