APPLICATION OF CARBON NANOTUBES IN DRUG DELIVERY :APPLICATION OF CARBON NANOTUBES IN DRUG DELIVERY Alberto Bianco1, Kostas Kostarelos2 and Maurizio Prato3, 1Institute of Molecular and Cellular Biology, UPR 9021 CNRS, 67084 Strasbourg, France2Centre for Drug Delivery Research, The School of Pharmacy, University of London, London WC1N 1AX, UK3Department of Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy MOHANA MARIMUTHU


PRESENTATION OUTLINE :PRESENTATION OUTLINE Introduction Method Results and discussion -Peptide delivery by CNT -Cellular uptake by CNT -Nucleic acid delivery by CNT -Drug Delivery with CNT Conclusion


INTRODUCTION :INTRODUCTION CNT-Vaccine delivery systems or protein transporters CNT synthetic methods- SWNT AND MWNT Pristine CNT – insoluble Soluble CNT – several application


Scanning electron microscopy (SEM) images of pristine single- (left) and multi-walled (right) carbon nanotubes. :Scanning electron microscopy (SEM) images of pristine single- (left) and multi-walled (right) carbon nanotubes.


METHOD :METHOD 2 funtionalization approaches 1.oxidation 2.Addition reaction 1,3-dipolar cyclo addition of azomethine ylides CNT + α-amino acid + an –CHO DMF f-CNT F-CNT linked to active molecules


Slide 6:Figure 2. Organic functionalisation of carbon nanotubes. Pristine single- or multi-walled carbon nanotubes can be (a) treated with acids to purify them and generate carboxylic groups at the terminal parts, or (b) reacted with amino acid derivatives and aldehydes to add solubilising moieties around the external surface.


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION PEPTIDE DELIVERY BY CNT B-cell epitope of FMDV + -NH3gp on CNT FMDV peptide-nanotube assessed in vivo in mice high antibody response interact with complement


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION II. CELLULAR UPTAKE OF CNT CNT with fluorescent agent epifluorescence and confocal microscopy Passive and endocytosis Protein-CNT in endosomes incubated Hela cells


Slide 9:Figure 3. Ultrathin transverse section of HeLa cells treated with functionalized MWNT. After incubation, the cells were fixed stained,dehydrated and embedded into an epoxy resin (Epon® 812). Ultrathin layers (90 nm thickness) were sliced with a diamond ultramicrotome and inspected under TEM. White arrows indicate the f-CNT distributed into the cytoplasm.


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION CNT at cell membrane Nanoneedles Nanotube spearing MCF-7 breast cancer cells


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION III. NUCLEIC ACID DELIVERY BY CNT Ammonium f-CNT WITH Nucleic acid enhance gene transfer and expression plasmid DNA pCMV- Bgal on –NH3 f-CNT CNT with PEI


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION Ammonium CNT condense ODN Immunostimulating activity Mouse splenocytes CNT deliver non-coding RNA polymers into cells Diverse application


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION IV. DRUG DELIVERY WITH CNT multiple functionalization of CNT MWNT with amphotericin-B and fluorescein Antifungal activity C.albican, C.parapsilosis, Cryptococcus neoformans


Slide 14:Figure 4. Functionalisation and imaging of CNT with amphotericin B. (a) Covalent attachment of amphotericin B and fluorescein isothiocyanate to CNT. Multi-walled carbon nanotubes are treated with acids to generate carboxylic groups, subsequently modified with a mono- protected diaminotriethylene glycol. The nanotubes are then subjected to 1,3-dipolar cycloaddition. Selective cleavage of the orthogonal protecting groups allows the introduction of the fluorescein moiety and amphotericin B. (b) Epifluorescence microscopy image of f-CNT inside Jurkat cells. Bright-field image (left) and fluorescent image (right) after internalisation of f-CNT incubates for 16 h at 37 °C. Jurkat cells have an average diameter of 10 μm.


RESULTS AND DISCUSSION :RESULTS AND DISCUSSION SWNT with substituted carborane cages Boron neutron capture therapy Single walled carbon Nanohorns With dexamethasone Experiment in mouse


DRUG DELIVERY WITH CNT :DRUG DELIVERY WITH CNT


CONCLUSION :CONCLUSION Organic funtionalization Factors -Bio-compatibility -solubility in physiological media high propensity to cross cell membrane interesting and deserve further investigation


THANK YOU FOR YOUR PATIENCE :THANK YOU FOR YOUR PATIENCE