NANOMEDICINE FOR CARCINOMAN.DEEPAK VENKATARAMAN FIRST M.PHARM PHARMACOLOGY

C.L.BAID METHA COLLEGE OF PHARMACY CHENNAI

FLOW OF PRESENTATION

INTRODUCTION NANOMEDICINE BASED DRUG DELIVERY IN CANCER LIPOSOME DENDRIMER GOLD NANOSHELL QUANTUM DOT FULLERENE CLINICALLY APPROVED NANOPARTICLE - BASED THERAPEUTICS NANOPARTICLE BASED THERAPEUTICS IN CLINICAL TRIALS FUTURE OF NANOMEDICINE CONCLUSION

INTRODUCTION

CANCER IS A DREADED DISEASE

VIDEO PATHOGENESIS OF CANCER

How cancer develops.flv

SHORTCOMINGS OF EXISTING FORMULATIONS AVAILABLE IN THE MARKET Poor bioavailability Not site specific more adverse effects less potent

EMERGING TECHNOLOGY THE NANOTECHNOLOGY

TECHNOLOGICAL DEVELOPMENTS OF THE LAST HALF CENTURY

Outline of developments: 1. In the middle of the 40s, TRANSISTORS and SEMICONDUCTORS were developed.

2.In the early 60s, LASER (light amplification by stimulated emission of radiation) was invented.

3.In the early 70s, integrated circuits(ic) and personal computers(pc) were developed

4.In the early 80s, superconductors were revived. Many medical instruments were built, such as MRI(Magnetic Resonance Imaging)

5.The most current development: Nanotechnology. .Has Numerous applications in various fields such as electronics, physics, chemistry, engineering, material sciences and most importantly medicine.

What is NANOMEDICINE ?My focus will be on the applications of nanomedicine in cancero

Nanomedicine may be defined as the monitoring, repair, construction , and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures. 1nano=10-9m.

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NANOMEDICINE BASED DRUG DELIVERY IN CANCER

MOLECULES THAT WERE DEVELOPED AS NANODEVICES FOR TARGETED ACTION

LIPOSOMES

Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules Liposomes are artificially prepared vesicles made of lipid bilayer. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Liposomes can be prepared by disrupting biological membranes, for example by sonication.

APPLICATIONS OF LIPOSOMES

Name Liposomal amphotericin B Liposomal amphotericin B

Trade name Abelcet

Company Enzon

Indication Fungal infections Fungal and protozoal infections Malignant lymphomatous meningitis HIV-related Kaposis sarcoma Combination therapy with cyclophosphamide in metastatic breast cancer

Ambisome

Gilead Sciences

Liposomal cytarabine

Depocyt

Pacira (formerly SkyePharma)

Liposomal daunorubicin

DaunoXome

Gilead Sciences

Liposomal doxorubicin

Myocet

Zeneus

Liposomal IRIV vaccine Liposomal IRIV vaccine

Epaxal Inflexal V

Berna Biotech Berna Biotech SkyePharma, Endo

Hepatitis A Influenza Postsurgical analgesia Age-related macular degeneration, pathologic myopia, ocular histoplasmosis HIV-related Kaposis sarcoma, metastatic breast cancer, metastatic ovarian cancer Menopausal therapy

Liposomal morphine DepoDur

Liposomal verteporfin

Visudyne

QLT, Novartis

Liposome-PEG doxorubicin

Doxil/Caelyx

Ortho Biotech, Schering-Plough

Micellular estradiol

Estrasorb

Novavax

LIPOSOMES IN CANCER THERAPY

Another interesting property of liposomes are their natural ability to target cancer. The endothelial wall of all healthy human blood vessels is encapsulated by endothelial cells that are bound together by tight junctions. These tight junctions stop any large particles in the blood from leaking out of the vessel. Tumour vessels do not contain the same level of seal between cells and are diagnostically leaky. This ability is known as the Enhanced Permeability and Retention effect.

Liposomes of certain sizes, typically less than 200 nm, can rapidly enter tumour sites from the blood, but are kept in the bloodstream by the endothelial wall in healthy tissue vasculature. Anticancer drugs such as Doxorubicin, Camptothecin and Daunorubicin are currently being marketed in liposome delivery systems. New Liposomal drugs targeting cancer like Liposomal Cisplatin has received Orphan Drug designation for Pancreatic Cancer.

DENDRIMER

Dendrimers are repetitively branched molecules A dendrimer is typically symmetric around the core, and often adopts a spherical threedimensional morphology. A dendron usually contains a single chemically addressable group called the focal point.

THE DIFFERENCE BETWEEN DENDRONS AND DENDRIMERS IS ILLUSTRATED IN FIGURE

APPLICATIONS OF DENDRIMER

DENDRIMERS ARE USED IN

DRUG DELIVERY GENE DELIVERY SENSORS

DRUG DELIVERY

The use of dendrimers as drug carriers by encapsulating hydrophobic drugs is a potential method for delivering highly active pharmaceutical compounds that may not be in clinical use due to their limited water solubility and resulting suboptimal pharmacokinetics

GENE DELIVERY

Current research is being performed to find ways to use dendrimers to traffic genes into cells without damaging or deactivating the DNA.

SENSORSFullerene is used to 1.detect fluorescence signal quenching 2.metal cation photodetection

DENDRIMER IN CANCER THERAPY

The dendrimer enhances both the uptake and retention of compounds within cancer cells.

GOLD NANOSHELL

A nanoshell is a type of spherical nanoparticle consisting of a dielectric core which is covered by a thin metallic shell (usually gold). These nanoshells involve a quasiparticle called plasmon which is a collective excitation or quantum plasma oscillation where the electrons simultaneously oscillate with respect to all the ions

APPLICATIONS OF GOLD NANOSHELL

Nanoshells possess highly favourable optical and chemical properties, often used for biomedical imaging, therapeutic applications, fluorescence enhancement of weak molecular emitters, surface enhanced Raman spectroscopy and surface enhanced infrared absorption spectroscopy

GOLD NANOSHELL IN CANCER THERAPY

Gold nanoshells are shuttled into tumours by the use of phagocytosis where, phagocytes engulf the nanoshells through the cell membrane to form an internal phagosome, or macrophage. After this it is shuttled into a cell and enzymes are usually used to metabolize it and shuttle it back out of the cell. These nanoshells are not metabolized, so for them to be effective they just need to be within the tumour cells and photo induced cell death is used to terminate the tumour cells.

DESTROYING TUMOUR CELLS USNIG GOLD COATED NANOSHELLS.

. BY DIAGNOSING THE AREA OF THETUMOURS ,THE GOLD COATED NANOSHELLS ARE INJECTED INTO THAT PARTICULAR AREA.THEN PASSING THE U.V. LIGHT ON THOSE NANOSHELLS IT BECOMES HEATED AND TUMOUR CELLS ARE DESTROYED WITHOUT EFFECTING NORMAL CELLS.

.THE TUMOUR CELLS ARE DESTROYED AT430C WHEREAS NORMAL CELLS GET DESTROYED AT 490C.

GOLD NANOSHELL IN CANCER THERAPY VIDEO

Gold Nanoparticles and Cancer Cell Detection.flv

QUANTUM DOTS

quantum dots are semiconductors whose electronic characteristics are closely related to the size and shape of the individual crystal. Generally, the smaller the size of the crystal, the larger the band gap, the greater the difference in energy between the highest valence band and the lowest conduction band becomes, therefore more energy is needed to excite the dot, and concurrently, more energy is released when the crystal returns to its resting state.

THERAPEUTIC APPLICATIONS OF QUANTUM DOTS

quantum dots for highly sensitive cellular imaging Improved photo stability helps in constructing high resolution 3 dimensional image extraordinary photo stability of quantum dot probes is the real-time tracking of molecules and cells over extended periods of time

Antibodies, streptavidin, peptides, nucleic acid aptamers, or small-molecule ligands can be used to target quantum dots to specific proteins on cells Semiconductor quantum dots have also been employed for in vitro imaging of pre-labeled cells. The ability to image single-cell migration in real time is expected to be important to several research areas such as embryogenesis, cancer metastasis, stem-cell therapeutics, and lymphocyte immunology.

QUANTUM DOTS IN CANCER

First attempts have been made to use quantum dots for tumor targeting under in vivo conditions. There exist two basic targeting schemes: 1.active targeting and 2.passive targeting. Active targeting, quantum dots are functionalized with tumorspecific binding sites to selectively bind to tumor cells. Passive targeting utilizes the enhanced permeation and retention of tumor cells for the delivery of quantum dot probes. Fast-growing tumor cells typically have more permeable membranes than healthy cells, allowing the leakage of small nanoparticles into the cell body. Moreover, tumor cells lack an effective lymphatic drainage system, which leads to subsequent nanoparticle-accumulation

QUANTUM DOT APPLICATIONS FOR CANCER MANAGEMENT.

QUANTUM DOTS

Quantum dot labelling of mouse colon cancer

FULLERENE

A fullerene is any molecule composed entirely of carbon, in the form of a hollow sphere, ellipsoid, or tube. Fullerenes are similar in structure to graphite, which is composed of stacked graphene sheets of linked hexagonal rings; but they may also contain pentagonal (or sometimes heptagonal) rings.

APPLICATIONS OF FULLERENE

anticancer drug delivery systems using photodynamic therapy, HIV drugs, and cosmetics to slow down the aging of human skin.

FULLERENE IN CANCER THERAPY

fullerene-antibody(ZME-018)

conjugate target the melanoma antigen found on the surface of melanoma cells.

CLINICALLY APPROVED NANOPARTICLE BASED THERAPEUTICS

NANOPARTICLE BASED THERAPEUTICS IN CLINICAL TRIALS

FUTURE OF NANOMEDICINE

FUTURE OF NANOMEDICINE - VIDEO

nanomedicine nanotechnology for cancer treatment.flv

CONCLUSION

ADVANTAGES OF NANOMEDICINES OVER MARKET AVAILABLE FORMULATIONS

Increased bioavailability. Targeted drug delivery. Less adverse reactions. Can used in the Diagnosis of cancer Increased drug efficiency.

Thus it is conclusive that nanomedicine will definitely be a MILESTONE in the treatment of CARCINOMA.

REFERENCES1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Popular Science Wikipedia American Scientist Electronics for you Physics for you Electronics Education www.foresight.org www.nanotech-now.com www.nanorevolution.com www.nanotech.org