carbon nano tubes for delivery of anticancer drugs
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Transcript of carbon nano tubes for delivery of anticancer drugs
Carbon Nanotubes for delivery of Anticancer Drug
Presented by
Rameshwar Madharia
PE/2013/313
Guided by
Dr. Wahid Khan
Assistant Professor
Department of Pharmaceutics
Introduction
Carbon Nanotubes
Pros and Cons of CNTs
Current research on CNTs
Drug selection and profile
Objective
Formulation development
Characterization
References
List of Contents
Life threatening disease, cancer, continues to increase with increasing age of the
population and urbanization.
In a number of situations, the malignancy of tumors is detected only at advanced
stages when administration of chemotherapeutic drugs is toxic to healthy cells.
In the attempt to improve this condition, the approaches to explore targeted drug
delivery and detect cancer cells at an early stage are of particular interest.
Carbon nanotubes (CNTs) having properties such as their potential
biocompatibility in pharmaceutical drug delivery systems and their excellent role
as drug carriers with a highly site-selective delivery and sensitivity make them
good drug carrier.
Introduction
Cancer is a broad group of disease involving unregulated cell-growth.
In cancer, cells divide & grow uncontrollably, forming malignant tumors,
which may invade nearby parts of body.
Treatment of cancer
Chemotherapy
Radiation
Surgery
Palliative care
Cancer
wikipedia.org/wiki/Cancer#cite_note-1
•.
Cancer Scenario in India
Source: Year wise total cancer prevalence in India [ICMR, 2006; ICMR, 2009]
•Cancer is one of the leading causes of death in India.
• About 2.5 million cancer patients in india.
• 1 million new cases added every year.
•A chance of the disease rising five-fold by 2025.
Carbon Nanotubes (CNT)
L. Lacerda et al. / Advanced Drug Delivery Reviews 58 (2006) 1460–1470
•Carbon nanotubes (CNT) consist exclusively of carbon atoms arranged in a series of condensed benzene rings rolled-up into a tubular structure.
• This novel nanomaterial belongs to the family of fullerenes, the third allotropic form of carbon along with graphite and diamond.
Carbon nanotubes (CNT) consist exclusively of carbon atoms arranged in a series of condensed benzene rings rolled-up into a tubular structure.
Their name is derived from their long, hollow structure with the walls formed by one-atom-thick sheets of carbon, called graphene.
These sheets are rolled at specific and discrete ("chiral") angles, and the combination of the rolling angle and radius decides the nanotube properties.
Components of CNT
Classification
consist of one layer of cylinder graphene.
have diameters from 0.4 to 2.0 nm.
lengths in the range of 20–1000 nm.
contain several concentric graphene sheets.
with diameters in the range of 1.4–100 nm
lengths from 1 to several μm.
L. Lacerda et al. / Advanced Drug Delivery Reviews 58 (2006) 1460–1470
Single-walled (SWNT)
•Consist of one layer of cylinder graphene.
•Have diameters from 0.4 to 2.0 nm.
•Lengths in the range of 20–1000 nm.
Multi-walled (MWNT)
•Contain several concentric graphene sheets.
•With diameters in the range of 1.4–100 nm.
•Lengths from 1 to several μm.
CNT have very interesting physicochemical properties such as:
Ordered structure with high aspect ratio
Ultralight weight
High mechanical strength
High electrical conductivity
High thermal conductivity
Metallic or semi-metallic behaviour and
High surface area
The combination of these characteristics make CNT a unique material with the
potential for diverse applications, including biomedical.
Pros of CNT
L. Lacerda et al. / Advanced Drug Delivery Reviews 58 (2006) 1460–1470
Hydrophobicity
Production of structurally and
chemically reproducible
batches
Bundling/aggregation of
individual tubes
Cons of CNT
Functionali-zation Overcome by
L. Lacerda et al. / Advanced Drug Delivery Reviews 58 (2006) 1460–1470
Scientists are just now beginning to explore uses for nanotubes in the medical field.
Fluorescent nanotubes will eventually be utilized for specific anti-cancer treatments involving the ejection of tiny fluorescent light particles.
Additionally, scientists are interested in the injection of nanotubes into the human body to act as actuators or substrates for cell cultures or implants.
The use of nanotubes in technologically advanced wound dressings is also in progress. Research thus far has shown a connection between accelerated wound healing when materials similar to nanotubes are present.
Current research on CNTs
Doxorubicin (Trade name Adriamycin) is a drug used in cancer chemotherapy & derived by chemical semisynthesis from a bacterial species.
It is an anthracyclin antibiotic, it works by intercalating DNA base pairs & inhibit the synthesis of DNA.
Commonly used in the tretmaent of blood cancers like leukemia & lymphoma & many types of carcinoma(solid tumors) & soft tissue sarcomas.
In spite of high clinical effectiveness against many cancers due to side-effects, effective & safer way of delivery of DOX is needed.
Drug-SelectionDoxorubicin(DOX)
B.S. Wong et al. / Advanced Drug Delivery Reviews 65 (2013) 1964–2015
Physico-chemical Properties of Doxorubicin
drugbank.ca/drugs/DB00997
Property Value
State Red crystalline solid
Melting point 229-231 °C
Log P 1.27
Stability Stable under normal conditions. Light, moisture sensitive.
Solvent solubility Soluble in normal saline, methanol, acetonitrile. Practically insoluble in acetone, benzene, chloroform, ethyl ether and petroleum ether.
pKa 9.53
In spite of their high clinical effectiveness against many cancers, the use of anthracyclines is unfortunately plagued with-
Myelosuppression, Alopecia, Acute nausea and vomiting, Vesicant effects and, Most notably, cardiotoxicity.
More effective and safer ways of delivering anthracyclines are hence of significant research interest.
Limitation of Doxorubicin
B.S. Wong et al. / Advanced Drug Delivery Reviews 65 (2013) 1964–2015
The objective is to synthesize Carbon nanotubes based drug delivery system for anticancer drug Doxorubicin through which the controlled & targeted delivery of drug can be achieved & also to reduce the side-effects of drug.
Objective
Selection of Materials
Purification of SWCNTs
Synthesis of biofunctionalized chitosan
Loading of SWCNTs with DOX
Synthesis of DOX-loaded CNT-chitosan-folate carrier
Formulation Development
H. Huang et al. / Advanced Drug Delivery Reviews 63 (2011) 1332–1339
Fourier transform infrared (FTIR) spectra
UV spectra
Scanning electron microscopy(SEM)
Drug loading efficiency
Drug release response
Fluorescence spectra
Characterization
H. Huang et al. / Advanced Drug Delivery Reviews 63 (2011) 1332–1339
H. Huang et al., A new family of folate-decorated and carbon nanotube-mediated drug delivery system: Synthesis and drug delivery response, Advanced Drug Delivery Reviews,63 (2011),1332–1339.
B.S. Wong et al., Carbon nanotubes for delivery of small molecule drugs, Advanced Drug Delivery Reviews,65 (2013),1964–2015.
L. Lacerda et al., Carbon nanotubes as nano medicines: From toxicology to pharmacology, Advanced Drug Delivery Reviews,58 (2006),1460–1470.
A. Battigelli et al., Endowing carbon nanotubes with biological and biomedical properties by chemical modifications, Advanced Drug Delivery Reviews, 65 (2013), 1899–1920.
References
Z. Liu et. al., Carbon materials for drug delivery & cancer therapy, Materials Today, July-august 2011,Volume 14,Number 7-8.
Y. Zhang et. al., Functionalized carbon nanotubes for potential medicinal applications, Drug Discovery Today, June 2010,Volume 15, Numbers 11-12.
C.P. Firme III, P.R. Bandaru, Toxicity issues in the application of carbon nanotubes to biological systems, Nanomedicine: Nanotechnology, Biology, and Medicine,6 (2010),245–256.