Nanomedicine

A brief presentation on Nanomedicine including history, diagnostics and therapeutics along with toxicology

1. NANOMEDICINE: Therapeutics & Toxicology By: Dr. Shruthi Rammohan 2 nd Year PG Pharmacology RRMCH

2. Why Nano? SMALL is the new BIG

3. Nanoparticle Applications Industrial Healthcare & Medicine Electronics & Computers Food & Agriculture Textiles Environment

4. Outline INTRODUCTION THERAPEUTICS NANOTOXICOLOGY FUTURE VISION

5. “ Nano ” A prefix meaning “extremely small” Translates to “one billionth” Greek origin “ nanos ” meaning “dwarf” Denotes a factor of 10 -9 or 0.000000001

6. Terminology NANOTECHNOLOGY The use and application of materials with sizes in the nanometer range NANOPARTICLE A microscopic particle of matter that is measured on the nanoscale (1 to 100 nanometers) NANOMEDICINE The branch of medicine concerned with the use of nanotechnology

7. One NANOMETER is to a TENNIS BALL , what a TENNIS BALL is to PLANET EARTH Tennis Ball Planet Earth

8. Nanoscopic Scale NANOTECHNOLOGY UTILIZES MATERIALS BELOW 1,000 NANOMETERS !!!

9. Just as a millimeter is one-thousandth of a meter , a nanometer is one-millionth of a millimeter Diameter of Human hair = 80,000 nanometers Red Blood Cells = 8,000 nanometers NANOTECHNOLOGY UTILIZES MATERIALS BELOW 1,000 NANOMETERS !!! Nanoscopic Scale

10. Nanoscale Materials  Increased Surface Area Greater amount of material is in contact with surrounding materials  HIGH REACTIVITY

11. History of Nanomedicine Fathers of Nanomedicine Richard Feynman Norio Taniguchi K. Eric Drexler

12. History of Nanomedicine December 29 th , 1959, Physicist Richard Feynman gave a radical lecture at an American Physical Society meeting at Caltech University entitled “There’s Plenty Of Room At The Bottom.” Feynman suggested that it should be possible to make machines at the nanoscale that “arrange the atoms the way we want” and do chemical synthesis by mechanical manipulation This lecture was the birth of the idea and study of nanotechnology

13. History of Nanomedicine Professor Norio Taniguchi of the Tokyo Science University introduced the term “Nanotechnology” in 1974 “Nanotechnology”- Processing, separation, consolidation and deformation of materials by one atom or by one molecule

14. History of Nanomedicine In the 1980’s, Dr. K. Eric Drexler promoted the nanoscale phenomena through books: Engines of Creation: The Coming Era of Nanotechnology Nanosystems : Molecular Machinery, Manufacturing and Computation Ultimately responsible for the term nanotechnology to acquire its current sense

15. Nanotechnology in Hollywood Hollywood came out with a movie in 1966 that provided the public with a glimpse of the future of nanoscience “Fantastic Voyage” Depicts a miniaturized surgical team that was injected into a man to operate on a blood clot in his brain

16. A new branch in pharmacology that is rapidly emerging It is the application of nanotechnology to the development and discovery of drug delivery methods Target Drug Delivery Diagnostically Therapeutically Nanopharmacology

17. Conventional Therapy Nanopharmacology Decreased bioavailability Wide and non-specific distribution Increased systemic toxicity Increased risk/benefit ratio Drug Resistance Protection of molecule from metabolism and degradation Able to reach specific target site Reduced systemic toxicity Risk/benefit ratio ??? Lower/Infrequent dosing

18. Ultimate Goal Nanomedicine is the application of nanotechnology to achieve breakthroughs in healthcare Enables early detection and prevention of diseases A new era of treatment and therapy Overall  Improve diagnosis and treatment Comprehensive monitoring , control and repair - Of all human biological systems (molecular level) - Using engineered devices and nanostructures - To achieve medical benefit

19. Nanomedicine Interdisciplinary field of science Nanomedicine Biology Nano - technology Chemistry

20. Applications Imaging Identification Delivery of medication to exact location Killing bacteria, viruses and cancer cells Repair of damaged tissues DIAGNOSTIC THERAPEUTIC

21. Diagnostic: Imaging Nanoparticles are being used extensively as contrast agents in non-invasive medical imaging tools CTs MRIs PETs Ultrasound Optical imaging Agents used: Nanosized metal oxides Dendrimers Quantum dots

22. “Lab-on-a-chip”- In-vitro diagnostics based on a nanoscale Advantages: Applications - Reduced costs - Heart Disease - Portability - Insulin Detection - Shorter and faster analysis Diagnostic: Identification

23. “Lab-on-a-chip” to monitor lithium medication levels at home for manic depressive patients Diagnostic: Identification Size of postage stamp Lower cost Greater convenience

24. Colloidal gold particles – rapid tests for pregnancy and ovulation Gold shell particles – biomedical imaging Magnetic nanoparticles – cell sorting in clinical diagnostics Silica nanoparticles – diagnostic imaging Superparamagnetic iron oxide nanoparticles – MRI Magnetic iron oxide nanoparticles – detection of Alzheimer plaques Other Diagnostic Applications In The Market

25. Drug Delivery forms under investigation Dendrimers Nanoshells Liposomes Micelles Quantum Dots Nanocrystals Therapeutic: Drug delivery with nanoparticles

26. Dendrimers Manmade molecules Tree like structure many small branching molecules around a central core molecule 2-20 nm Applications : Cancer cell recognition Diagnosis of cancer Drug delivery Reporting drug levels in tumors Reporting cancer cell death

27. Dendrimers Examples: Doxorubicin IV Flurbiprofen IV Methotrexate IV Piroxicam IV

28. Nanoshells Core of silica with metallic outer layer (usually gold) Linked to antibodies that recognize tumor cells Application: Once the cancer cells take up the nanoshells , an infrared light is applied and taken up by the nanoshells . Intense heat is created which selectively kills the tumor cells only and not the neighboring healthy cells

29. Liposomes Small spherical vesicles 200 nm or smaller Lipid bilayer Applications : Targeted drug delivery Cancer treatment

30. Liposomes Examples: Amikacin IV Amphotericin B IV Doxorubicin IV Paclitaxel IV Prednisolone IV

31. Micelles Lipid molecules that arrange themselves in a spherical form in an aqueous solution Amphiphilic Hydrophobic core and hydrophilic shell Hydrophobic core serves as a reservoir for drug molecules

32. Micelles Examples: Doxorubicin IV Paclitaxel IV Pilocarpine Ocular Tranilast Oral Micelles easily loaded with wide variety of poorly water soluble drug  enhanced bioavailability Target drug delivery Targeting achieved by attaching specific ligands or antibodies onto surface

33. Nanocrystals Examples: Rapamycin Fenofibrate Paclitaxel Silver P ure solid drug particles with a size in the nanometer range Does not consist of any matrix material

34. Quantum Dots Type of nanocrystal 2-10 nm 20 times brighter and 100 times more stable than traditional fluorescent dyes

35. Quantum Dots Quantum Dots Drug Delivery & Cancer Diagnostic Imaging

36. Quantum Dots Applications Microscopy and multiplexed histology Flow cytometry Cellular Imaging (real-time intracellular events and cellular tracking) Tissue mapping and demarcation (Sentinel node) Tumor Targeting/Staging Drug delivery

37. Doxorubicin Methotrexate Flurbiprofen Piroxicam Paclitaxel Amikacin Amphotericin B Prednisolone Vitamin D₃ Nanodrugs

38. Applications CANCER PAIN SUNSCREEN AGENTS ANTIBIOTICS VITAMIN D DENTAL CERAMICS

39. Nanotoxicology Branch of nanoscience dealing with the study and application of the toxicity of nanomaterials

40. “DOUBLE EDGED SWORD”

41. Key Factors in the Interaction with Biological Systems: Size & Shape Surface Area Nanoparticle dose Solubility Nanotoxicology

42. INCREASED TOXICITY DUE TO QUANTUM SIZE EFFECTS As particle size decreases, surface area to volume ratio increases  highly active Nanotoxicological studies intended to determine to what extent these properties pose a threat to human beings Nanotoxicology

43. Oxidative Stress PRIMARY CAUSE OF NANOTOXICITY  Induced production of Reactive Oxygen Species DNA damage Apoptosis Inflammation Accumulation of Nanoparticles Nanoparticles that don’t dissolve easily accumulate in different parts of the body and persist  Toxic effects of a particular organ system Molecular Mechanisms

44. ?

45. Nanotoxicology

46. Nanoparticle Application Toxicity Silica Nanoparticles Ceramic Nanoparticles Superparamagnetic Iron Oxide Nanoparticles Gold Shell Nanoparticles Titanium dioxide Silver Nanoparticles Carbon Nanoparticles Drug Delivery Diagnostic Imaging Cancer Drug Delivery MRI contrast Cancer Drug Carriers Biomedical Imaging and Therapeutics Cancer Therapeutics Antibacterial Agents Drug Dellivery Platelet Aggregation -Reproductive Toxicity -Oxidative Stress - Cytotoxic Activity- Lungs, Liver, Heart and Brain -Oxidative Stress -Disturbance in iron homeostasis -Hepatic and Splenic Toxicity -CNS Toxicity -ER Stress Response -Pulmonary Toxicity -Intestinal Inflammation

47. ADVANTAGES Reduced degree of invasiveness Reduced systemic side effects of drugs Cost effectiveness of medical & surgical therapy Benefits in cancer therapy Reduced morbidity and mortality rates DISADVANTAGES Lack of proper knowledge about nanoparticle effects on biochemical pathways and processes of the human body Toxicity Different effects of drugs due to particle size Difficulty in ADR monitoring Advantages & Disadvantages of Nanomedicine

48. Nanorobots … A future vision To detect/repair targeted damage and infections Biomedical instrumentation Nanosurgery

49. Concluding Statement Full potential of nanomedicine may be years or even decades away Recent advances in nanotechnology related diagnosis, drug delivery and drug development are beginning to change healthcare management Nanotherapy could be more economically convenient , effective and safe ENDLESS POSSIBILITIES… ONLY TIME WILL TELL

50. References: The British Society for Nanomedicine http://www.britishsocietynanomedicine.org/what-is-nanomedicine.html Khanna P., Ong C., Bay BH., Baeg GH. Nanotoxicity : An Interplay of Oxidative Stress, Inflammation and Cell Death. Nanomaterials . 2015. (5) 1163-80 Review: Quantum Dots and Application in Medical Science Satyanarayana V., Bhandare B., Adhikary J. Nanotechnology: Medical Applications and Health Hazards. Journal of Medical Sciences. 2013. 1(1) 5-10 https://copublications.greenfacts.org/en/nanotechnologies/l-2/6-ealth-effects-nanoparticles.htm http://images.sciencesource.com/p/16352255/Quantum-Dots-Malaria-Progression-JC2688.html Nanomedicine : Meaning, Advantages and Disadvantages “Disadvantages of Nanomedicine ” http://mhs-nanomedicine.weebly.com/disadvantages-of-nanomedicine.html

51. Nanomedicine … the future of medicine Thank You!