Carbon Nanotubes (CNTs) for

Transdermal Drug Delivery

İsmail Tuncer Değim

Univ. of Connecticut, School of Pharmacy, Storrs, CT 06269, USA

Present address: Gazi University, Faculty of Pharmacy, Ankara, Turkey

09-11-2008 Ankara
Do CNTs penetrate and is it unsafe
to work with?
• Single-walled carbon nanotubes (SWCNTs) and
multiwalled carbon nanotubes (MWCNTs) can
be internalized by living skin cells,

• Their penetrations through stratum corneum

and their drug carrying properties
through the skin have not been
investigated.

L. Lacerdaa et al., Nanotoday 2:38 (2007).

N.A. Monteiro-Riviere et al., Nanotoxicology 1:293 (2005).
Human skin
Carbon nanotubes
• Discovered in 1952
(Radushkevich and
Lukyanovich),
• Produced and observed under a
variety of conditions around
SWCNTs
1991.
DWCNTs and MWCNTs

The interlayer distance is

approximately 3.3 Å
 Model Drugs
• Indomethacin:
Hydrophobic drug
Log Ko/w = 4.5, pKa=4.5

• Doxorubicin:
Water soluble drug, pKa=8.4
Indomethacin experiments
Penetration of indomethacin through
full thickness rat skin

Flux values:
Indomethacin alone=0.119+0.037µg/h
Indomethacin with MWCNTs=0.330+0.052µg/h
Indomethacin with DWCNTs=0.347+0.106µg/h (n=3,SD)
Indomethacin adsorption on CNTs

3.8 mg CNTs and 10 mg drug was used.

 Iontophoresis
• Franz type diffusion cells were used,
• Electrodes were Ag/AgCl, current was 0.5
mA/cm2,
• Samples were collected at different time intervals
and analyzed by HPLC.

Preparation of drug containing electrodes:

Indomethacin and MWCNTs dried at 55°C. CNTs
containing indomethacin were fixed to the
surface of electroconductive carbon stickers
(Pelco Tabs 12 mm OD) and attached to silver
chloride wire and used as the cathode.
These results indicate that MWCNT has functionalized about 0.735 - 0.953%
and MWCNT-PEG contains about 7.792 – 13.124% PEG-3350.
Physical appearance of MWCNTs
under SEM
AFM
Why some of CNTs are not straight?

MWCNTs are much stronger !

Penetration through pig ear skin
MWCNTs

Pig skin after MWCNTs exposure

Indomethacin solubility
Doxorubicin experiments
 Doxorubicin

1mg CNTs and 0.482mg Doxorubicin were used.

Penetration process:
Possible interactions with skin
lipids
Can CNTs interact with skin lipids?
Can they stay among the lipids?
 Can CNTs alter the fluidity of skin
lipids?

F o r m u l a t i o n DPPC ( m g) D W CNT (µg) M W CNT (µg) PG ( m l ) W a t er ( ml )

1 2 0 0 0.1 1

2 2 25 0 0.1 1

3 2 50 0 0.1 1

4 2 75 0 0.1 1

5 2 100 0 0.1 1

6 2 500 0 0.1 1

7 2 0 25 0.1 1

8 2 0 50 0.1 1

9 2 0 75 0.1 1

10 2 0 100 0.1 1

11 2 0 500 0.1 1
Visualization of penetration process:
 Conclusions
• CNTs are suitable for drug transport having higher surface area and
being an adsorptive material,

• The CNTs investigated can not penetrate through skin, their

penetration enhancement is by adsorption and subsequent
desorption (i.e. depot effect),

• CNTs can be useful to increase transdermal penetration for especially

hydrophobic drugs,

• The application of iontophoresis is also possible using CNTs as

adsorptive electrodes and they can be used for both water soluble or
insoluble compounds.
Thank you…
 Acknowledgements

Prof.Dr. Diane J. Burgess

Prof.Dr. Fotios Papadimitrakoplis

TUBITAK
Scientific and Technological
Research Council of Turkey

Gazi University, Faculty of

Pharmacy, Dept. of
Pharmaceutical Technology,
Ankara, Turkey