CARBON NANOTUBE IN ANTICANCER DRUG DELIVERY.pptx

carbon nanotube used in cancer treatment

1. CONTENT Introduction Chemistry of nanotubes Synthesis Drug delivery targeted to tumor Pharmacokinetic Role of ph Toxicity Types of cnt Application Mode of breakdown of cnt Advantages Disadvantages Conclusion

2. 1. 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 have led to much excitement in the field of pharmacy. High Thermal conductivity. Excellent electron emission characterstics . ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy.  Good candidates for a wide variety of applications, including drug transporters, new therapeutics, delivery systems and diagnostics. It is discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery.

3. 2. Chemistry of nanotubes sidewall End tip

4. Carbon nanotube chemistry  involves  chemical reactions , which are used to modify the properties of  carbon nanotubes  (CNTs). The two main methods of CNT functionalization are covalent and non-covalent modifications. (A) COVALENT MODIFICATION It attaches a functional group onto the carbon nanotube. The functional groups can be attached onto the side wall or ends of the carbon nanotube. OXIDATION This processes were essential for low yield production of carbon nanotubes where amorphous carbon  particles and coatings comprised a significant percentage of the overall material and are still important for the introduction of surface functional groups. During acid oxidation, the carbon-carbon bonded network of the graphitic layers is broken allowing the introduction of oxygen units in the form of  carboxyl ,  phenolic  and  lactone  groups, which have been extensively exploited for further chemical functionalization .

5. ESTERIFICATION  AND  AMIDATION  REACTIONS. The carboxylic group is converted into an acyl chloride with the use of thionyl or  oxalyl chloride  which is then reacted with the desired amide, amine, or alcohol. Carbon nanotubes have been deposited on with  silver nanoparticles  with the aid of amination reactions. CYCLOADDITION Controlled functionalization of carbon nanotubes (CNTs) through the use of cycloaddition reactions is described. By employing various cycloaddition reactions, a wide range of molecules could be coupled onto CNTs without disruption of the structural integrity as well as with a statistical distribution of functional groups onto the surface of the CNTs. The cycloaddition reactions represent an effective and tailored approach for preparing CNT-based advanced hybrid materials that would be useful for a wide range of applications from nanobiotechnology to nanoelectronics

6. (B) NON-COVALENT MODIFICATIONS Non-covalent modifications do not disrupt the natural configuration of carbon nanotubes with the cost of chemical stability, and is prone to phase separation. POLYNUCLEAR AROMATIC COMPOUNDS Some common polynuclear aromatic compounds that are functionalized with hydrophilic or hydrophobic moieties are used to solubilize carbon nanotubes into organic or aqueous solvents. Some of these  amphiphiles  are  phenyl ,  naphthalene ,  pyrene  and  porphyrin  systems. The greater π-π stacking of aromatic amphiphiles such as pyrene amphiphiles had the best solubility compared to phenyl amphiphiles with the worse π-π stacking, lead to more solubility in water.

7. Π-Π STACKING AND ELECTROSTATIC INTERACTIONS Molecules that have bifunctionality are used to modify the carbon nanotube. One end of the molecule are polyaromatic compounds that interact with the carbon nanotube through π-π stacking. The other end of the same molecule has a functional group such as amino, carboxyl, or thiol. The greater π-π stacking of aromatic amphiphiles such as pyrene amphiphiles had the best solubility compared to phenyl amphiphiles with the worse π-π stacking, lead to more solubility in water. MECHANICAL INTERLOCKING A particular case of non-covalent modification is the formation of rotaxane-like mechanically interlocked derivatives of  single-walled nanotubes (SWNTs)  In this strategy, the SWNTs are encapsulated by molecular macrocycle(s), which are either formed around them by macrocyclizatioor pre-formed and threaded at a later stage.

8. 3. Synthesis of carbon nanotube

9. T he oldest method for the carbon nanotube production is the electric arc discharge. This technique was used already in the early sixties by R. Bacon for the synthesis of carbon fibres called whiskers. The same technique was adapted in 1990 by Krätschmer and Huffman to produce fullerenes in good yields, and later on this method was improved and applied for the synthesis of multiwall (MWNT) and singlewall (SWNT) carbon nanotubes. Other methods such as the laser evaporation/ablation and chemical vapour deposition (CVD) were also succesfully examined in the production of carbon nanotubes. The laser evaporation process is technically similar to the arc discharge method. The difference between these two methods is in the quality and purity of the obtained products.

10. METHOD ARC DISCHARGE METHOD LASER METHOD CHEM. VAPORIZATION METHOD PROCESS it involves two graphite electrode in presence of helium and a current of 50 ampere is passed through two graphite electrodes this process consist of graphite rods and it contain 50:50 catalyst mixture of Co and Ni at 12000C and argon is flowing through it in this process reaction chamber contain mixture of nitrogen, ethylene and acetylene. during this temperature of reaction chamber was 700-9000C and one atmospheric pressure. CONDITION Low pressure inert gas Argon gas at 1200*c 700-900*c temp at one atmospheric pressure YIELD 32-91% UPTO 70% UPTO 100% CARBON SOURCE Graphite Graphite Hydrocarbon COST High High Low

11. 4. DRUG DELIVERY TARGETED TO TUMOR To deliver anticancer drugs into cancer focus is the prerequisite for the drugs to develop their effects. However, some drugs cannot arrive or enter cancer tissues because of their short residence time in blood circulation. For example, the efficacy of paclitaxel (PTX), a widely used chemotherapeutic agent in cancer therapy, is often limited by its poor solubility in aqueous medium and nonspecific cytotoxicity, thereby preventing it from efficiently reaching the cancer focuses.  Furthermore, the solubilizer cremophor in current formulation (Taxol) has exhibited allergenic activity, prompting the search for alternative delivery systems. For this purpose, Liu et al. successfully conjugated Paclitaxel to branched Polyethyleneglycol chains on SWCNTs via a cleavable ester bond to obtain a water-soluble SWCNT-PTX complex. In a murine 4T1 breast cancer model, the SWCNT-PTX complex showed an efficacy higher than that of the clinically used Taxol in suppressing tumor growth. 

12. 5 . PHARMACOKINETIC OF CARBON NANOTUBES IN CANCER  Surface coating or functionalizing the CNTs has huge effects on their pharmacokinetics, ADME properties and also their biodistribution profile. After administration, absorption is the first key step for drug carriers to complete their drug- delivering mission. Studies have suggested that CNTs themselves are capable of being absorbed. CNTs that are orally administered can be absorbed through the columnar cells of intestinal mucous membrane, where this was confirmed by transmission electron microscopy . The absorbed CNTs are transported from the administration sites to the effect-relevant sites by blood circulation. Both SWCNT and MWCNT were found to be excreted through the renal route and observed to be intact in the excreted urine by transmission electron microscopy.

13. 6 . ROLE OF PH ON THE SOLUBILITY OF CARBON NANOTUBES  Strong acid treatments could give rise to carboxylic functionalization of CNTs, but damage their structure and decrease their thermal stability. Their residual yields after acid treatments decreased, whereas the concentrations of the COOH groups increased, with increasing temperature or time of the acid treatment. 7. TOXICITY Under some conditions,  nanotubes can cross membrane barriers, which induce harmful effects such as inflammatory and fibrotic reactions. Under certain conditions CNTs can enter human cells and accumulate in the cytoplasm causing cell death. The process by which CNTs were synthesized and the types and amounts of metals they contained, CNTs were capable of producing inflammation, epitheloid granulomas (microscopic nodules) fibrosis and biochemical/toxicological changes in the lung

14. 8. TYPES OF CARBON NANOTUBES (CNTS) The carbon nanotubes are of two types namely: Single walled carbon nanotubes (SWCNTs) Multiple walled carbon nanotubes (MWCNTs) (A) SWCNT s consist of a single cylindrical carbon layer with a diameter in the range of 0.4-2 nm, depending on the temperature at which they have been synthesized. The structure of SWCNTs may be arm chair, zigzag, chiral, or helical arrangements The SWCNTs have an ultrahigh surface area as large as 1300 m2/g, which renders sufficient space for drug loading and bio conjugation . In drug delivery, SWCNTs are known to be more efficient than MWCNTs. This is due to the reason that SWCNTs have ultrahigh surface area and efficient drug-loading capacity.

15. (B) MULTIWALL CARBON NANOTUBES (MWCNTs) MWCNTs consist of several coaxial cylinders, each made of a single grapheme sheet surrounding a hollow core. The outer diameter of MWCNTs ranges from 2-100 nm, while the inner diameter is in the range of 1-3 nm, and their length is one to several micrometers Decoration of multiwall carbon nanotubes (MWCNTs) consists of depositing nanoparticles on the MWCNT walls or ends, bonded by physical interaction with potential applications in catalysis, biosensors, biomedical, magnetic data storage, and electronic devices

16. APPLICATION OF CARBON NANOTUBE IN CANCER Carbon nanotubes are used in drug delivery carriers for treatment of cancer. And they are reported for targeting of amphotericin B to cells. Carbon nanotubes are used for generation of tissue. In recent years carbon nanotubes are best for tissue generation because these are biocompatible, resistant to biodegradation and enhancing the organ generation Carbon nanotubes are used as energy storage devices. Carbon nanotubes are used in artificial implants. carbon nanotubes having high tensile stregth so they are filled with calcium and arranged like a bone, so can acts as a bone substituent. Carbon nanotubes are antioxidant in nature so they are used preserve drugs that are easily oxidized. Carbon nanotubes are used for Gene therapy by DNA delivery. Gene therapy is a therapy to cure the gene which can causeharmful disease by introducing DNA into cells.

17. ARTIFICIAL IMPLANT ENERGY STORAGE DEVICES

18. 10. MODE OF BREAK  DOWN OF CARBON NANOTUBE IN THE BODY Carbon nanotubes were once considered bio-persistent in that they did not break down in body tissue or in nature. In human’s a considerable time after exposure has shown for the first time that carbon nanotubes can be broken down by an enzyme- Myelo peroxidase (MPO) -- found in white blood cells. This enzyme is expressed in certain types of white blood cell (neutrophils), which use it to neutralize harmful bacteria.

19. 11. ADVANTAGES OF CARBON NANOTUBES Biocompatible, Non-biodegradable nature. Highly elastic nature and have the possibility of intracellular delivery. May exhibit minimum cytotoxicity. Excreted by urine 96% and remaining 4% by faeces. Ultra-light weight CNTs are able to enter cells by spontaneous mechanism due to its tubular and nano needle shape. It has distinct inner and outer surface, which can he differentially modified for chemical/ biochemical functionalization.

20. 12. DISADVANTAGES OF CARBON NANOTUBES It is difficult to maintain high quality and lower impurities. Cost of nanotechnology is very high . In ARC DISCHARGE and LASER method huge amount of energy is required to complete the process. It is difficult to target large amount of graphite in industrial process.

21. CONCLUSION Nanoparticulate as drug delivery systems is designed to improve the pharmacological and therapeutic properties of conventional drugs. The incorporation of drug molecules into nanocarrier can protect a drug against degradation as well as offers possibilities of targeting and controlled release. In comparison with the traditional form of drugs, nanocarrierdrug conjugates are more effective and selective; they can reduce the toxicity and other adverse side effects in normal tissues by accumulating drugs in target sites. In consequence, the required doses of drugs are lower. However, so far, the scientific paradigm for the possible (adverse) reactivity of nanoparticles is lacking and we have little understanding of the basics of the interaction of nanoparticles with living cells, organs and organisms. A conceptual understanding of biological responses to nanomaterials is needed to develop and apply safe nanomaterials in drug delivery in the future. Furthermore a close collaboration between those working in drug delivery and particle production is necessary for the exchange of concepts, methods and know-how to move this issue ahead.

22. REFERENCE Valentin N. Popov "Carbon nanotubes: properties and application" Materials Science and Engineering R 43 (2004) 61–102 B.K. Kaushik and M.K. Majumder, Carbon Nanotube Based VLSI Interconnects, SpringerBriefs in Applied Sciences and Technology, DOI 10.1007/978-81- 322-2047-3_2 Peter J.F. Harris “ Carbon nanotubes science : Synthesis, properties and applications” www.cambridge.org/9780521828956. p.no. 3 Kalpna Varshney "Carbon Nanotubes: A Review on Synthesis, Properties and Applications" International Journal of Engineering Research and General Science Volume 2, Issue 4, June-July, 2014 ISSN 2091-2730 A. Aqel , K.M.M. Abou El-Nour R. A.A. Ammar ,A. Al- Warthan"Carbon nanotubes, science and technology part (I) structure, synthesis and characterisation"Arabian Journal of Chemistry (2012) 5, 1–23 Iijima S, Ichihashi T. Single-shell carbon nanotubes of 1-nm diameter. Nature, 363, 603 (1993).

23. Brenner, D. ―Empirical potential for hydrocarbons for use in simulating the chemical vapor deposition of diamond films.‖ Physical Review B 42(15): 9458-9471, 1990 Calvert, P. ―Strength in disunity.‖ Nature 357: 365-366, 199 Kaushik, B.K, Majumder, M.K. "Carbon Nanotube: Properties and Applications" 2015,XI, 86 P, 57 illus., softcover. ISBN: 978-81-322-2046-6 Sinnott, S.B.; Andrews, R. Carbon Nanotubes: Synthesis, properties and applications. Critical Reviews in Solid State Mat. Sci. 26, 145–249, 2001. Mamalis AG, Vogtländer LOG, Markopoulos A. Nanotechnology and nanostructured materials: trends in carbon nanotubes. Precis Eng, 28, 16 (2004). Li WZ, Xie SS, Qian LX, Chang BH, Zou BS, Zhou WY, Zhao RA, Wang G. Large-scale synthesis of aligned carbon nanotubes. Science, 274, 1701 (1996). Xie S, Li W, Pan Z, Chang B, Sun L. Carbon nanotube arrays. Mater Sci Eng A, 286, 11 (2000). Ibrahim Khan "Carbon nanotubes- Properties and Applications: A Review" Article Carbon letters. July 2013 DOI: 10.5714/CL.2013.14.3.131 W. Zhang, Z. Zhang, and Y. Zhang, “The application of carbon nanotubes in target drug delivery systems for cancer therapies,” Nanoscale Research Letters, vol. 6, pp. 555–577, 2011 Y. Rosen and N. M. Elman, “Carbon nanotubes in drug delivery: focus on infectious diseases,” Expert Opinion on Drug Delivery, vol. 6, no. 5, pp. 517–530, 20