Uploaded byDr. Ashutosh Tiwari
Nanomedicine
Nanomedicine is an interdisciplinary field that uses nanotechnology for medical applications. It aims to diagnose, treat, and prevent disease at the molecular level using nano-scale tools. The document outlines the history of nanomedicine from Richard Feynman's 1959 talk introducing nanotechnology to current applications. Key applications discussed include drug delivery using nanoparticles like liposomes, imaging contrast agents, and miniaturized medical devices. Challenges also remain around potential toxicities of nanomaterials.
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Nanomedicine
- 2. Nanomedicine DR. ASHUTOSH TIWARI 2NDYEAR PG RESIDENT PHARMACOLOGY DEPARTMENT SAIMS 2
- 3. Outline • Introduction tonanomedicine • History & Timeline • Applications of nanomedicine • Advantages and disadvantages • Challenges • Conclusion 3
- 4. Nanomedicine: an interdisciplinaryfield of science Nanomedicine Biology ChemistryNanotechnology 4
- 5. Introduction Human bodyis basically an extremely complex system of interacting molecules (i.e., a molecular machine) therefore technology required to truly understand and repair the body is the molecular machine technology : nanotechnology 5
- 6. Nanoscale Nanoscience: involvesresearch and technology development at 1 nm to 100 nm range (nanoscale) “nano” indicates 10-9 A nanometre is 10-9 meter. one nanometre is a billionth of a metre or a millionth of a millimetre a single human hair is around 80,000 nanometres thick A typical protein size lies between 3 to 10 nanometres (nm) red blood cells are a standard size of about 6000‐8000 nm 6
- 7. Nanomedicine: Definition Theofficial definition of the US National Nanotechnology Initiative says that nanotechnology involves ‘research and technology development at the atomic, molecular, or macromolecular levels, in the length scale of approximately 1 to 100 nm range. European Science Foundation (ESF) has defined nanomedicine as ‘the science and technology of diagnosing, treating and preventing disease and traumatic injuries, of relieving pain, and improving human health, using molecular tools and molecular knowledge of human body 7
- 8. Aim of Nanomedicine comprehensive monitoring, control, construction, repair, defence and improvement of all human biological systems, working from the molecular level using engineered devices and nanostructures, ultimately to achieve medical benefit. 8
- 9. History On December29, 1959, physicist Richard Feynman gave a radical lecture at an American Physical Society meeting at Caltech titled “There’s Plenty of Room at the Bottom”. Feynman suggested that it should be possible to make machines at a nano- scale 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. 9
- 10. History Professor NorioTaniguchi of the Tokyo Science University, introduced the term “nanotechnology”, in 1974 He described nanotechnology as the processing of, separation, consolidation, and deformation of materials by one atom or by one molecule." 10
- 11. History In the1980s, Dr. K. Eric Drexler, promoted nanoscale phenomena through books: Engines of Creation: The Coming Era of Nanotechnology Nanosystems: Molecular Machinery, Manufacturing, and Computation He was ultimately responsible for the term nanotechnology to acquire its current sense. he was presented the first PhD in nanotechnology. 11
- 12. History Hollywood providedthe public with a glimpse of the future of nano- science with the release of the film Fantastic Voyage in 1966, which depicted a surgical team that was miniaturized and injected into a man to operate on a blood clot in his brain 12
- 13. History Bhasma, isa ayurvedic metallic/mineral preparation, treated with herbal juices or decoction and exposed for certain quantum of heat as per puta system of Ayurveda Bhasma are claimed to be biologically produced nanoparticles (ethno-nanomedicine) 13
- 14. Nanotechnology: Timeline Inearly 2003, the European Science Foundation launched its Forward look on nanomedicine; a policy briefing was published on 23rd February 2005 which summarised the recommendations of the Forward Look. In 2004 High Level Group European Technology Platform Nanomedicine was launched In September 2005, its Vision Paper and Basis for a Strategic Research Agenda for Nanomedicine was released, as a first step towards setting up a European Technology Platform on Nanomedicine in 2007, the European Foundation for Clinical Nanomedicine was established in Basel (Switzerland) 14
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- 16. Nanotechnology: Timeline TheUS National Institutes of Health (NIH) released their first roadmap on nanomedicine in 2004 In 2004, the National Cancer Institute (NCI), as part of NIH, launched the Cancer Nanotechnology Plan, a strategic initiative to transform clinical oncology and basic research through the directed application of nanotechnology 16
- 17. First successful nanomedicine:Abraxane 17
- 18. Current status Themarket analysis reported that market for the nanomedicine is continuously growing at the rate of 28 % with a 35% increase in the revenues generated The National Science Foundation estimated the market for all nanotechnologies to be $1 trillion. Huge investments are being made in nanomedicine to develop novel therapeutic deliveries. Currently more than 38 nanomedicine based products are on the market with estimated sales of $6.8 billion and the efforts to bring them on the market are increasing continuously 18
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- 20. Application of Nanomedicine •Diagnostic Imaging and identification • Therapeutic Delivering medication to the exact location. Killing of bacteria, viruses & cancer cells Repair of damaged tissues. 20
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- 22. Diagnostic use: Imaging Nanomaterials are being used extensively as contrast agents in non-invasive medical imaging tools, including computed tomography, magnetic resonance, positron emission tomography, single photon- emission computed tomography, ultrasound, and optical imaging The contrast agents used: nanosized metal oxides, dendrimers, quantum dots, etc. 22
- 23. Diagnostic Use: Imagingusing Quantum dots Quantum dots Nano crystals (nano cadmium & nano zinc) are semiconductors used to tag biological molecules have applications in medical diagnostics, targeted therapeutics, and high-throughput drug screening tiny crystals, produce sequence of colours when subjected to ultraviolet rays 23
- 24. Diagnostic use Currentlyin vitro diagnostics are costly and it is hoped that new generation nanoscale “lab-on- a- chip” will offer advantages including reduced costs, portability, and shorter and faster analysis. Applications may include measurements of saliva for periodontitis, heart disease, insulin detection and improving healthcare accessibility 24
- 25. Diagnostic tools alab-on-a- chip with the size of a postage stamp is already commercially available and is used to monitor lithium medication levels for manic depressive patients at home at much lower cost and with greater convenience Other diagnostic applications using nanotechnology and already on the market include: colloidal gold particles which, due to their stability, have been widely used to rapidly test for pregnancy, ovulation, HIV and other indications magnetic nanoparticles used for cell sorting applications in clinical diagnostics superparamagnetic iron oxide nanoparticles for magnetic resonance imaging – first approved in Europe in 1993 Magnetic iron oxide nanoparticles also show great promise in the detection of Alzheimer plaques 25
- 26. Medical instruments Medicalinstruments are also being increasingly miniaturised, with nanomaterials for increased efficiency carbon nanotubes may be used instead of glass pipettes for delivery into cells Nanosilver is increasingly incorporated into catheters and other instruments as a coater because of its antimicrobial effects Wound dressings may also incorporate some sort of nanosilver, for the same purpose 26
- 27. Therapeutic uses: Drugdelivery using Nanoparticles Nanopharmacology: an application of nanotechnology to the development and discovery of drug delivery methods. Application to deliver Medication to the exact location. Lesser side effects & high efficacy Improves bio-availability Molecular targeting by nano engineered devices 27
- 28. Therapeutic uses: Drugdelivery using Nanoparticles Nanoformulations of existing drugs can overcome common pharmaceutical problems by increasing solubility, limiting systemic toxicities, increasing bioavailability and improving immuno- compatibility and cellular uptake Nanotechnology has also been used for targeted drug delivery which will allow controlled drug release at just the right place and dose, improving patient safety and compliance and reducing side effects. Drug delivery vehicles under investigation include: polymeric particles, dendrimers, nanoshells, liposomes, micelles and magnetic nanoparticles 28
- 29. Therapeutic uses: Drugdelivery using Nanoparticles Advantages & of a targeted drug delivery system Encapsulation of a drug (such as in a liposome or micelle) can avoid local irritation and decrease local and systemic toxicity, Disadvantages The drug delivery mechanisms may also introduce toxicities of their own and have unintended side effects. 29
- 30. Therapeutic uses: Drugdelivery using Nanoparticles Metal-based nanoparticles – Au, Ag, Cd-Se, Zn-S etc Lipid-based nanoparticles – Liposome & Neosome based Polymer-based nanoparticles – Dendrimer, chitosen, micelle based Biological nanoparticles – arginylglycylaspartic acid (RGD) peptides based 30
- 31. Liposomes Liposomes aresmall spherical vesicles, composed of lipid bilayers surrounding aqueous inner phase Liposomes are usually composed of phospholipids or cholesterol, which are used to encapsulate various active drugs. At the target site liposomes fuse with the cell membranes and deliver the molecules Liposomes are 200 nm or smaller Applications targeted drug delivery cancer treatment Some liposome based pharmaceuticals: Amphotericin B, Daunorubicin, Doxorubicin, Amikacin 31
- 32. PEGylated Liposomes PEG(polyethylene glycol) makes the liposome less vulnerable to immune system PEGylation, by increasing the molecular weight of a molecule, can impart several significant pharmacological advantages over the unmodified form, such as: Improved drug solubility Enhanced protection from proteolytic degradation Increased drug stability Extended circulating life Reduced dosage frequency, without diminished efficacy with potentially reduced toxicity 32
- 33. Niosomes Niosomes, non-ionicsurfactant vesicles, widely studied as an alternative to liposomes similar to liposomes in terms of their physical properties Niosomes alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and high cost. They have the potential for controlled and targated drug delivery Niosomes enhance the penetration of drugs 33
- 34. Dendrimers Dendrimers aremanmade molecules having a tree like structure having number of small branching molecules around a central core molecule. Dendrimers measure between 2-20 nanometers across and are branching molecules with the branching beginning at the core. Nano devices based on dendrimers may be used for cancer cell recognition, diagnosis of cancer cause, drug delivery, reporting drug levels in tumors and reporting cancer cell death. 34
- 35. Nano shells Nanoshells have a core of silica and a metallic outer layer. Nano shells can be linked to antibodies that can recognize tumor cells Once the cancer cells take them up, by applying a near infra red light that is absorbed by the Nano shells, it is possible to create intense heat that selectively kills the tumor cells and not the neighboring healthy cells 35
- 36. Carbon nanotubes Single-wallcarbon nanotubes are tiny hollow rods that are one-atom-thick 10,000 times smaller in diameter than a human hair extraordinary optical, mechanical, thermal and electronic properties being used to produce lightweight and extremely strong materials, which enhance the capabilities of devices such as sensors, and provide a novel means of delivering drugs with great specificity. 36
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- 44. FDA Approved nanodrugs Liposomes: Amphotericin B, Daunorubucin, Doxorubicin, Cytarabine, Morphine, Amikacin Emulsions: Cyclosporin A Engineered nanoparticales: Diclofenac Polymeric nanoparticles: Paclitaxel Nanocrystals: Rapamycin, Aprepitant, Fenofibrate, Megestrol, Fenofibrate 44
- 45. Drug discovery Nanoand micro technologies are part of the latest advanced solutions for decreasing the discovery and development times for new drugs, and potentially reducing the development costs. High-throughput arrays and ultra-sensitive labeling and detection technologies are being used to increase the speed and accuracy of identifying genes and genetic materials for drug discovery and development. 45
- 46. Therapeutic uses: Cancer treatment Thermotherapy, a form of cancer treatment that uses heat to destroy cancer cells. By using nanoparticles to generate the heat, the treatment can be more successfully localised and result in fewer side effects. The devices use a number of different nanomaterials including nanosized iron oxides, gold-coated silica nanoparticles and hafnium oxide nanoparticles 46
- 47. Tissue repair &replacement Implant coatings: biocompatible nanomaterials and coatings to increase the adhesion, durability and lifespan of implants. For example, nanopolymers such as polyvinyl alcohol (PVA) can be used to coat implantable devices that are in contact with blood (e.g. artificial hearts, vascular grafts, catheters) for dispersing clots or preventing their formation 47
- 48. Tissue repair &replacement Tissue Regeneration Scaffolds Nanostructures are being researched for the preparation and improvement of tissue regeneration scaffolds For example, PVA is also being investigated for the cornea by having corneal epithelia cells seeded in a PVA hydro gel structure. Structure implant materials for Bone repair: e.g. High strength nanoceramic materials, such as calcium phosphate apatite (CPA) and hydroxyapatite (HAP) 48
- 49. Nanorobots – Afuture vision • Nanorobots are nanodevices. • Potential applications include • To repair or detect targeted damages and infections. • early diagnosis and targeted drug delivery for cancer, • biomedical instrumentation, surgery 49
- 50. “A microscopic machine roaming throughthe bloodstream, injecting or taking samples for identification and determining the concentrations of different compounds” 50
- 51. “A single inhaled Nanorobot reaches, deeply inspired into thelungs and attaches to the tissue surface” 51
- 52. “Mechanical drilling of a smalltumor mass by a nanorobot” 52
- 53. A nanorobot nibbling onan atherosclerotic deposit in a blood vessel 53
- 54. Advantages of nanomedicine • Drug delivery to the exact location. • Lesser side effects, high efficacy • Molecular targeting by nano engineered devices • Detection / Diagnosis of diseases relatively easy & fast • No surgery required. • Diseases can be easily cured. 54
- 55. Disadvantages • Not practicalyet. • High cost. • Implementation difficulties. • Nanotoxicity 55
- 56. Nanotoxicity The nanoparticlescan have off target effects such as triggering an immune response, crossing blood brain barrier and affecting CNS or can cause tissue toxicity if not properly eliminated Several toxicological responses of nanomedicine based on in-vivo characterization have been reported such as hypersensitivity reactions, element specific toxicity and generation of reactive oxygen species for example multiwalled carbon nanotubes (MWCNT) were found to cause asbestos- like effects on the mesothelium following intracavitary injection of high doses in rodents. 56
- 57. Nanotoxicity In 2006,there was a disaster during the clinical trial phase-I study; 6 healthy volunteers were recruited and administered with TGN 1412 (CD 28 MAB) intended for the treatment of rheumatoid arthritis and lymphocytic leukaemia. It was humanised monoclonal antibody and CD 28 receptor agonist. The drug was administered as intravenous infusion and within half an hour all the subjects suffered from life threatening conditions. So it was concluded that in-vivo behaviour in animals is not a true representation of humans and more work is need to be done to reduce the risks involved in the clinical trials 57
- 58. Nanotoxicity There isa need for a detailed examination of the physico- chemical properties of nanoparticles such as size, shape and surface chemistry and correlating them with their in-vivo behaviour could help in understanding the most important technical issues and also for the development suitable models for studying nanotoxicity 58
- 59. Challenges posed by Nanomedicine Regulatory issues Environmental issues Social Issues Ethical issues 59
- 60. Regulatory issues Thereare two primary regulatory problems posed by nanomedicine: classification difficulties lack of scientific expertise The FDA classifies medical products for regulatory purposes as drugs, devices, biologics, or combination products In the long run, sophisticated nanomedical products will blur the distinction between “mechanical”, “chemical”, and “biological” and make it difficult to determine if a product is a drug, device, biologic, or combination product. Effective regulation requires that the FDA maintain expertise in cutting edge technologies and scientific advances 60
- 61. Environmental risks NationalScience Foundation and Environmental Protection Agency have raised concerns over potential impact of nanomaterials on the environment and the adverse effects have been reported The possible excretion mechanisms are suggesting that it would be mainly disposed in water and air. The excretory materials would mostly be suspended in air for longer times due to their small size which can cause respiratory disorders and affect the health of individuals 61
- 62. Social issues Firstly,the prices would be very high and the patients from the low income groups would be deprived of these novel therapeutics and the developing nations would be affected most. Nanomedicine will generate social and ethical debates regarding issues such as whether implantable nano-devices that can constantly monitor for illness compromise privacy rights and risk abuse whether neurobiochips that stimulate brain function give humans machine-like qualities and steer society on a path toward mental manipulation through implantable devices in the brain 62
- 63. Ethical issues Bioethicalresearchers believe that nanomedicine could be manipulated to harm the human body rather than healing it. How would the use of a technology that can’t be seen be regulated? What if, they say, the guiding system on the medicine malfunctions and takes the medicine to the wrong part of the body, such as the brain? What if the nanomedicine technology is used for terrorism purposes? Particles that can’t be seen or easily controlled would enter the body and deliver harmful substances such as toxins. Will the materials used for the nano-medicinal technologies be non-toxic and eco-friendly? 63
- 64. Conclusion • Although realizationof the full potential of nanomedicine may be years or decades away, recent advances in nanotechnology-related drug delivery, diagnosis, and drug development are beginning to change the landscape medicine. • The possibilities are endless, but will take time to develop. • Nano therapies could, in the long term, be much more economical, effective and safe and could greatly reduce the cost of current medical procedures. • So, Nanomedicine is the future medicine. 64
- 65. To conclude ….. RichardE. Smalley, PhD, 1996 Nobel Laureate, once said, “Human health has always been determined on the nanometer scale; this is where the structure and properties of the machines of life work in every one of the cells in every living thing. The practical impact of nanoscience on human health will be huge.” 65
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- 68. In the NearFuture: Humanoid Shaped Nanorobots! 68