nanobotics and their pharmaseutical aplications

S. Brito Raj et al. (2012) Int J of Ad Biomed & Pharm Res. 1(1): 43-54.

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International Journal of Advanced Biomedical & Pharmaceutical Research

An official Journal of Sri Venkateswara College of Pharmacy, Chittoor, A.P., India.

NANOROBOTICS AND THEIR PHARMACEUTICAL APPLICATIONS

S.Brito Raj1*, G.Sravani1, Nara Bhanupriya1, B.Rekha1, P.Sreekanth1, S.Wasim Raja2, and

K.Bhaskar Reddy1

1Department of Pharmaceutics, Sri Venkateswara College of Pharmacy, R.V.S. Nagar, Chittoor-517127(A.P) India. 2Department of Pharmacy Practice, Sri Venkateswara College of Pharmacy, R.V.S. Nagar, Chittoor-517127(A.P) India.

INTRODUCTION Nanotechnology

The origin of nanotechnology is often associated with the talk given by Nobel Prize winner Richard Feynman entitled “There’s Plenty of Room at the Bottom”. In this

talk, Feynman discusses the possibilities (i.e., in principle) of what is now commonly referred to as nanotechnology and how its advancement could potentially generate an enormous number of technical applications.

Nanotechnology contains technological developments on the nanometer scale, usually on the order of 0.1 to 100 nm. A nanometer is one billionth of a meter (1 nm = 10-9 m). For a perception of this scale at the atomic

Article Info Article history Received: 20/11/2012 Revised: 25/11/2012 Accepted: 28/11/2012 Keywords Nanoparticles, Nanorobots, Components, Drug Delivery Systems, Medical Nanorobots, Applications

ABSTRACT The origin of nanotechnology is often associated with the talk given by Nobel Prize winner Richard Feynman entitled “There’s Plenty of Room at the Bottom”. In this talk, Feynman discusses the possibilities (i.e., in principle) of what is now commonly referred to as nanotechnology and how its advancement could potentially generate an enormous number of technical applications. Doctors today can’t affect molecules in one cell while leaving identical molecules in a neighboring cell untouched because medicine today cannot apply surgical control to the molecular level. There are opportunities to design nanosized, bioresponsive systems able to diagnose and then deliver drugs, and systems able to promote tissue regeneration and repair (in disease, trauma and aging), circumventing chemotherapy. The long term goal is the development of novel and revolutionary bimolecular machine components that can be assembled and form multi-degree-of freedom nano devices that will apply forces and manipulate objects in the nanoworld, transfer information from the nano to the macro world, and travel in the nano environment. These machines are expected to be highly efficient, controllable, economical in mass production, and fully operational with minimal supervision. The emerging field of medical nanorobotics is aimed at overcoming these shortcomings. Molecular manufacturing can construct a range of medical instruments and devices with greater abilities. Ongoing developments in molecular fabrication, computation, sensors and motors will enable the manufacturing of nanorobots. These are theoretical nanoscale biomolecular machine systems within a size range of 0.5 to 3 microns with 1-100 nm parts. Work in this area is still largely theoretical, and no artificial non biological nanorobots have yet been built. These ultra miniature robotic systems and nano-mechanical devices will be the biomolecular electro-mechanical hardware of future biomedical applications.

Corresponding author Mr.S.Brito Raj E-Mail: [email protected]

http://www.ijabpr.com/


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level, a hydrogen atom’s diameter is on the order of an Angstrom (1 Å = 0.1 nm). Thus ten hydrogen laid side by side would measure a distance of about 1 nm across.

Nanotechnology is necessarily a multidisciplinary field which encompasses and draws from the knowledge of several diverse technological fields of study including chemistry, physics, molecular biology, material science, computer science, and engineering. Advances in the field of nanotechnology have expanded the breadth of potential applications tremendously in recent years. The nanotechnology research and development (R&D) areas have been growing rapidly throughout the world. Although its applied use is still limited, nanotechnology has already begun to appear in various applications and products, namely nanomaterials. According to information provided by the National Nanotechnology Initiative (NNI) website, nanomaterials are being used in a number of industries to improve product functionality for electronic, magnetic, optoelectronic, biomedical, pharmaceutical, cosmetic, energy, catalytic, and materials applications. In addition, it has been reported that the areas currently create the greatest revenue are the use of nanoparticles for chemical-mechanical polishing, magnetic recording tapes, sunscreens, automotive catalysts, biolabeling, electroconductive coatings and optical fibers. Although still considered to be in its infancy, breakthroughs in nanotechnology are expected to facilitate the development of other advanced applications in nanoelectronics, nanomedicine, nanoelectromechanical systems (NEMS), nanomaterials (e.g., nano composites) and nanorobotics.

A great deal of nanotechnology research in the U.S. comes under the purview of the National Nanotechnology Initiative (NNI) which provides a framework for government agencies to collaborate. The NNI focuses on nine Grand Challenge areas; one of these Grand Challenge areas targets robotics. It is of particular concern to the Intelligent Systems and Robotics Center (ISRC) to determine its role in the growing field of nanotechnology. Naturally and more specifically, the field of nanorobotics is the most important topic of interest to the ISRC and is discussed in greater detail in this report.(Couvreur P et al., 2006). Nanorobotics Nanorobotics, sometimes referred to as molecular robotics, is an emerging research area as evidenced by recent topics in the literature. In general, nanorobotics carries a variety of definitions throughout the literature. The field of nanorobotics can be generally divided into two main focus areas. The first area deals with the design, simulation, control, and coordination of robots with nanoscale dimensions (i.e., nanorobots). Nanorobots, nanomachines, and other nanosystems are objects with overall dimensions at or below the micrometer range and are made of assemblies of nanoscale components with individual dimensions ranging approximately between 1 to 100 nm. As

a result, nanorobots have for the most part been explored in the biological context of nanomedicine.

The second area deals with the manipulation and/or assembly of nanoscale components with macroscale instruments or robots (i.e., nanomanipulators). Due to the advances in nanotechnology and its rapidly growing number of potential applications, it is evident that practical technologies for the manipulation and assembly of nanoscale structures into functional nanodevices need to be developed. Nanomanipulation and nano assembly may also play a crucial role in the development of artificial nanorobots themselves. The main goal of this survey is to identify activities and advancement that have been made in this relatively new and emerging field (Cavalcanti A and Freitas RA et al., 2002; Cavalcanti A et al., 2007; Shirinzadeh B et al., 2007). Advantages

The process is very fast. Since the scale of operation is very small, the results are very accurate. The process is less painful unlike angioplasty, where the patient takes months to recover from the physical trauma of the operation. The process is technologically very advanced and reliable. The patient is not subjected to harmful rays unlike angioplasty where he is placed below a continuous X-ray during diagnosis. The chances of any after effects or recurrences are completely eliminated. Disadvantages

Nanorobots, the technology as such, may be very costly. The technology may take several years to be implemented practically. The technology may lead to further technological problems like the introduction of artificial reconstruction and artificial intelligence which will result in the robots going out of control of humans. Proposed Design of Nanorobots

The importance of nanosystems design for the investigation of nanorobots control has broken up recently as an important aspect for further research. Including aspects of the physical environment in conjunction with graphical visualization can provide a possible approach for Nanorobotics automation and control design. The nanorobots design is comprised of components such as molecular sorting rotors and a robot arm (telescoping manipulating arm) derived from biological models. The nanorobots exterior shape consists of a diamondoid material, which may be attached to an artificial glycocalyx surface which reduces fibrinogen, blood proteins adsorption and bioactivity, gives sufficient biocompatibility to evade immune system attack. Types of different molecules are distinguished by a sequence of chemo tactic sensors whose binding sites have a different affinity for each kind of molecule. The Nanorobot Control Design (NCD) simulator are used for the 3D investigation of a stenosed left anterior descending (LAD) coronary artery, in which we optimize the trigger for medical nanorobots. This trigger will turn the nanomachine “on”, switching it from “seek mode” to “repair


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mode”. It might also cause other close nanorobots switch to a “higher awareness mode”. Regarding knowledge about the general localization of the stenosis (in large, small or micro vessels), we may inject the suitable type of nanorobot , which is pre-programmed to be activated only at the pre-specified target area. The NCD simulator consists of numerous modules that simulate the physical conditions, run the nanorobot control programs shaping their actions, deliver a visual display of the environment in 3D, and trace the history of nanorobot behaviors for later analysis. (Freitas RA, 2005). Designing of Biological Nanorobot Biological nanorobots which are made of biological components, such as proteins, DNAs. Designing of bio

nanorobots implies nanorobots made up of bio components. The bio components offer immense variety and functionality at a scale where creating a man made material with such capabilities would be extremely difficult. Biocomponents seem to be logical choice for designing nanorobots. The core applications of nanorobots in the medical field and using Biocomponents for these applications seem to be good choice as they both offer efficiency and variety of functionality. Nanorobotics is a field which entitle for collaborative efforts between chemists, biologists, physicists, engineers, computer scientists and other specialists to work towards this universal objective. Fig. 1 details about the various fields which come under the bio nanorobotics. (Ignatyev MB, 2010).

Figure 1. Various Fields Which Come Under the Field of Bio Nanorobotics

NANO MATERIALS AND NANO DEVICES Liposomes

Liposomes discovered in mid 1960s were the original models of nanoscaled drug delivery devices. They can be used as effective drug delivery systems. Cancer chemotherapeutic is used as liposomal drugs produce much better efficacy and safety as compared to conventional preparations.

Immunoliposomes are liposomes conjugated along with an antibody and aimed towards the tumour antigen. Immunoliposomes when injected into the body, targets the tissue and gets accumulated in its specific site of action. This decreases unwanted effects and also increases the drug delivery to the target tissue, so that it enhancing its safety and efficacy. Antibody directed enzyme prodrug therapy (ADEPT) consists of liposomes conjugated with an enzyme to activate a prodrug and an antibody which target to a


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tumour antigen. These are administered previous to administration of a prodrug. Antibody directs the enzyme to the target tissue where it triggers the prodrug selectively and changes it to its active form. By this distribution of drug is avoided to the other normal tissues, thus reducing the toxicity of drug (Kirby C and Gregoriadis G, 1983). Tumor Targeting Immunoliposomes This method utilizes a tumor targeting antibody attached to the surface of liposomes incorporating the cancer drug. The surface of the immunoliposomes are also coated with a special chemical called polyethylene glycol (PEG) that protects them from being destroyed by the liver. The immunoliposomes are also made to be a certain size (about 100 nanometers) that makes them too large to pass thru the pores of normal blood vessels but small enough to pass thru the “leaky” blood vessels supplying the tumor. Once the immunoliposomes enter the tumor tissue the antitumor antibody binds to tumor antigens and fixes the immunoliposomes inside the tumor. In this way a high percentage of the immunoliposomes becomes concentrated within the tumor. The liposomes then break down releasing the cancer drug that will kill the surrounding tumor cells. The end result is that a high proportion of the cancer drug reaches the tumor for maximum effect and fewer drugs reaches normal tissues to cause harmful side-effects. The company proposes to formulate immunoliposomes utilizing its tumor targeting antibodies. For example, the HER 2 antibody is attached to immunoliposomes incorporating the cancer drug paclitaxel and used to treat breast cancers; and/or the anti tumor targeting antinuclear antibody is attached to immunoliposomes incorporating either the cancer drug paclitaxel or etoposide and used to treat a variety of solid tumors (Kirby C and Gregoriadis G, 1983). Nano Pores

A nanopore contains wafers with high density of pores with size 20 nm in diameter. The pores allow oxygen, glucose, insulin to pass through. It does not allow immunoglobulin and cells to pass through them. Nanopores can be used to protect transplanted tissues from the host immune system. β cells of pancreas was enclosed inside the nanopore device and implanted into the recipient’s body. This tissue sample gets the nutrients from the surrounding tissues and at the same time it remains not detected by the immune system and so it will not get rejected. This could provide as a newer modality of treatment for insulin dependent diabetes mellitus. Nanopores have the ability to distinguish DNA strands based on base pair sequences, purines and pyrimidines. Electricity conducting electrodes is being designed to improve longitudinal resolution for base pair identification which could possibly read a thousand bases per second per pore. It cost low with high throughput genome sequencing which would be of great advantage for

application of pharmacogenomics in drug development process (Deamer DW et al., 2000). Fullerenes Fullerenes are being inspected for drug transport of antibiotics, anticancer agents and antiviral drugs. Fullerenes are used as free radical scavengers due to existence of high number of conjugated double bonds in the core structure, which are found to have a protective activity against mitochondrial injury induced by free radicals. Fullerenes can also produce reactive oxygen species during photosensitization which can be used in cancer therapy (Thakral S and Mehta RM, 2006). Nanotubes Carbon nanotubes discovered in 1991 are tubular structures like a sheet of graphite rolled into a cylinder capped at one or both ends by a buckyball. Carbon nanotubes can be made more soluble by incorporation of carboxylic or ammonium groups to their structure and can be used for the transport of nucleic acids , peptides and other drug molecules. Indium-111 radionuclide labeled carbon nanotubes are being investigated for killing cancer cells selectively. (Tarakanov AO et al., (2009). Amphotericin B nanotubes has shown increased drug delivery to the interior of cells and a great efficacy as an anti-fungal agent compared to amphotericin B administration without nanotubes.The ability of nanotubes to transport DNA across cell membrane is used in studies involving gene therapy. It was found that carbon nanotubes, excluding acetylated ones, bonded with a peptide produce a higher immunological response compared to free peptides. so it can be used in vaccine production to improve the efficacy of vaccines (McDevitt MR et al., 2007). Quantum Dots Quantum dots are nanocrystals measuring about 2-10 nm which can be made to fluorescence when exposed by light. Quantum dots are used for biomedical purposes as a diagnostic and therapeutic tool. These can be attached with biomolecules, so that it can use as highly sensitive probes. Studies done on prostate cancer in nude mice has shown accumulation of quantum dots probe by increased permeability and retention as well as by antibody directed targeting. It can also used for imaging of sentinel node in cancer patients for planning of therapy and tumour staging. This method can be adopted for various malignancies like breast, melanoma, gastrointestinal and lung tumours. The application of quantum dots in a clinical setting has limitations due to its elimination factors. The working of the quantum dots which Protects from the toxic core, leads to enhance in size of the nanoparticle more than the pore size of renal capillaries and endothelium, so it reduces its elimination and resulting in toxicity. (Rapoport N et al., 2007).


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Nanoshells Nanoshells consist of nanoparticles with a core of silica which is coated with a thin metallic shell. These nanoshells can be targeted to desired tissue by immunological methods. This technology is being studied for cancer therapy. Nanoshells are at present being investigated for treatment of diabetes and also for micro metastasis of tumours. Nanoshells are used to diagnostic purposes in whole blood immunoassays. Gold nanoshells are coupled along with antibodies and the size can be changed so that it responds to NIR wavelength, which has the capacity to penetrate whole blood specimens. So that it is possible to detect immunoglobulins at a concentration range of nanograms per milliliter in plasma and whole blood. (Prato M et al., 2008) Nanobubbles Cancer therapeutic drugs can be incorporated in a nanoscaled bubble like structures called as nanobubbles. Nanobubbles remain stable at room temperature when it is heated to physiological temperature within the body coalesce to form microbubbles. The advantages of Nanobubbles are targeting the tumour tissue and deliver the drug selectively under the control of ultrasound exposure. It provides an advantage of enabling visualization of the tumour by means of ultrasound methods. Nanobubbles along with ultrasound exposure have shown increased transfer of gene in both in vitro, in vivo studies. Nanobubbles are also used as a therapeutic measure for removal of clot in vascular system in combination with ultrasound, which is called as sonothrombolysis. sonothrombolysis has advantages of being causing less damage to endothelium and noninvasive. (Pathak A et al., 2008). Paramagnetic Nanoparticles Paramagnetic nanoparticles are used as both diagnostic and therapeutic purposes. First of all diagnostically, paramagnetic iron oxide nanoparticles are used as distinct agents in magnetic resonance imaging. These targeted nanoparticles facilitate identification of specific organs and tissues. Magnetic microparticles probes with nanoparticle probes have been used for identification or detection of proteins like prostate specific antigen. Magnetic Nanopores are used in cancer therapy and also as diagnostic tool in cancers. Iron nanoparticles coated with monoclonal antibodies targeted to tumour cells are used to generate high levels of heat which kills the cancer cells effectively by accumulation of these nanoparticles in their target site by means of an externally applied alternating magnetic field. (Wang J, 2009). Nanosomes Nanosomes can be integrated with a photo catalyst which generate reactive oxygen species when stimulated by light and so that it destroys the target tissue. This method has

benefit over conventional drugs i.e., it is safer without the adverse effects of cancer chemotherapy drugs and also the absence of development of drug resistance. Nanosomes are being developed to integrate more and more components in it for flexibility of its applications. (Yarin AL, 2010). Dendrimers Dendrimers are nanomolecules with regular branching structures. The number of branching determines the size of the dendrimer which can be controlled. Tectodendrimers are complexes of dendrimers, with each dendrimer module of the complex performing different functions such as targeting, diagnosis of disease state, delivery of drug and imaging. This extended nanodevice has potential applications in cancer chemotherapy as a mode of targeted drug therapy. Dendrimers can be used for gene therapy where these can replace conventional viral vectors. The advantage of dendrimer based therapy is absence of stimulation of immune reaction. Dendrimers can also be used in treatment of cancer by conjugating with anti-cancer drugs like cisplatin, Adriamycin or methotrexate .The toxicity of dendrimer is dependent on the size of the particle and increase with size. It can be reduced by means of surface modification of the dendrimers with incorporation of PEG or fatty acids (Pan B et al., 2007). Respirocytes Respirocytes are hypothetical artificial red blood cells are nanodevices which can function as red blood cells but with greater efficacy. These have higher capacity to deliver oxygen to tissues, supplying 236 times more oxygen per unit volume than natural red blood cells. An infusion of one litre dose of 50 per cent Respirocytes saline suspension in a human can theoretically keep the patient oxygenated up to four hours following cardiac arrest. (Murphy D et al., 2007).

Figure 2. Respirocytes

Microbivores Microbivores are hypothetical structures which function as white blood cells in the blood stream designed to trap circulating microbes. They are expected to have greater efficacy than cellular blood cells in phagocytosis.


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Application of the microbivores in human circulation could theoretically clear the blood stream in septicaemia at a much greater rate than the natural defence mechanism with antibiotics (Freitas Jr RA, 2005b).

Figure 3. Microbivores

CONTROL OF NANOROBOTIC SYSTEMS The control of nano robotic systems could be

classified in two categories: i. Internal control mechanisms ii . External control mechanisms Nanomedicne

It is the application of nanotechnology (engineering of tiny machines) to the prevention and treatment of disease in the human bodies. More specifically, it is the use of engineered nanodevices and nanostructures to monitor, repair, construct and control the human biological system on a molecular level. The most elementary of nanomedical devices will be used in the diagnosis of illnesses. A more advanced use of nanotechnology might involve implanted devices to dispense drugs or hormones as needed in people with chronic imbalance or deficiency states. Lastly, the most advanced nanomedicine involves the use of Nanorobots as miniature surgeons. Such machines might repair damaged cells, or get inside cells and replace or assist damaged intracellular structures. At the extreme, nanomachines might replicate themselves, or correct genetic deficiencies by altering or replacing DNA (deoxyribonucleic acid) molecules. Introduce the device into the body. It is a need to find a way of introducing the nanomachine into the body, and allowing it access to the operations site without causing too much ancillary damage. The first is that the size of the nanomachine determines the minimum size of the blood vessel that it can traverse. We want to avoid damaging the walls of whatever blood vessel the device is in, we also do not want to block it much, which would either cause a clot to form, or just slow or stop the blood flow. What this means is that the smaller the nanomachine the better. However, this must be balanced against the fact that the larger the nanomachine the more versatile and effective it can be. This is especially important in light of the fact that external control problems become much more difficult if we are trying to use multiple machines, even if they don't get in

each other's way. The second consideration is we have to get it into the body without being too destructive in the first place. This requires that we gain access to a large diameter artery that can be traversed easily to gain access to most areas of the body in minimal time. The obvious candidate is the femoral artery in the leg. This is in fact the normal access point to the circulatory system for operations that require access to the bloodstream for catheters, dye injections, etc., so it will suit our purposes. Move the device around the body We start with a basic assumption: that we will use the circulatory system to allow our device to move about. We must then consider two possibilities: (a) carried to the site of operations (b) to be propelled. The first possibility is to allow the device to be carried to the site of operations by means of normal blood flow. There are a number of requirements for this method. We must be able to navigate the bloodstream; to be able to guide the device so as to make use of the blood flow. This also requires that there be an uninterrupted blood flow to the site of operations. In the case of tumors, there is very often damage to the circulatory system that would prevent our device from passively navigating to the site. In the case of blood clots, of course, the flow of blood is dammed and thus our device would not be carried to the site without the capability for active movement. Another problem with this method is that it would be difficult to remain at the site without some means of maintaining position, either by means of an anchoring technique, or by actively moving against the current. Nanomedicine can make possible the re-engineering of the human body, including the improvement of existing natural biological systems and the addition of new systems and capabilities not found in nature. Such re-engineering is commonly called "augmentation" (Kirby C and Gregoriadis G, 1983; Freitas RA, 2005a).

Figure 4. Implanted Nanocomputers Interface with the

Myriad Synapses of the Neurons of the Brain


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APPLICATIONS OF NANOROBOTS Tumors

We must be able to treat tumors; that is to say, cells grouped in a clumped mass. While the technique may eventually be used to treat small numbers of cells in lung tumor the bloodstream, the specified goal is to be able to destroy tumors tissue in such a way as to minimize the risk of causing or allowing a recurrence of the growth in the body. The technique is intended to be able to treat tumors that cannot be accessed via conventional surgery, such as deep brain (Wang J, 2009). Arteriosclerosis

This is caused by fatty deposits on the walls of arteries. The device should be able to remove it from the artery walls. This will allow for both improving the flexibility of the walls of the arteries and improving the blood flow through them. In view of the years it takes to accumulate these deposits, simply removing them from the artery walls and leaving them in the bloodstream should allow the body’s natural processes to remove the overwhelming preponderance of material (Cavalcanti A et al., 2002).

Figure 5. Nanorobots Recovering Arteriosclerosis

Blood Clots

The cause damage when they travel to the bloodstream to a point where they can block the flow of blood to vital area of the body. This can result in damage to vital organs in very short order. In many if not most cases, these blood clots are only detected when they cause a blockage and damage the organ in question, often but not always the brain. By using a micro robot in the body to break up such clots into smaller pieces before they have a chance to break free and move on their own (Freitas Jr RA, 1998). Kidney Stones

By introducing a micro robot into the urethra in a manner similar to that of inserting a catheter, direct access to the kidney stones can be obtained, and they can be broken up directly. This can be done either by means of ultrasonic directly applied, or by the use of a laser or other means of applying in intense local heat to cause the stones to break up

kidney stones (Murphy D et al., 2006; Cavalcanti A et al., 2007). Liver Stones

Liver stones accumulate in the bile duct. Micro robots of the above type can be introduced into the bile duct and used to Stone inside Liver Bile Ducts Break up the liver stones as well. By continuing on up the bile duct into the liver, they can clear away accumulated deposits of unwanted minerals and other substances as well. Burn and Wound Debriding

The micro robots can also be used to clean wounds and burns. Their size allows them to be very useful for removing dirt and foreign particles from incised and punctured wounds, as well as from burns. They can be used to do a more complete and less traumatic job than conventional techniques. Remove Tar in Lungs

They could be very useful for the treatment of dirty lungs. This could be done by removing particles of tar and other pollutants from the surface of the alveoli, and placing them where the natural processes of the body can dispose of them. This would require a micro robot capable of moving within the lungs, on alveolar surfaces as well as break down of tar over the mucus layer and over the cilia within the lungs. (Narayan RJ et al., 2004). Aging

DNA repair machines can repair or replace damaged or miscoded sections of chromosomes. Other medical nanorobots capable of cell repair can purge human tissue cells of unhealthy accumulated detritus and restore these cells to their youthful vigor. (Patel GM et al., 2010).

Figure 6. Nanorobots Reparing Damaged Cells

Artificial Blood and Respiration

Medical nanorobots can be employed as artificial oxygen carriers in the blood, thus assisting and extending normal human respiratory capacities. Hundreds of inhaled nanorobots rush through a large bronchial junction on their way deeper into the lungs as the patient takes a deep breath.


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Figure 7. Inhaled Nanorobotics

Drug Delivery

Nanotechnology provides a wide range of new technologies for developing customized solutions that optimize the delivery of pharmaceutical products. To be therapeutically effective, drugs need to be protected during their transit to the target action site in the body while maintaining their biological and chemicals properties. Some drugs are highly toxic and can cause harsh side effects and reduced therapeutic effect if they decompose during their delivery. Depending on where the drugs will be absorbed (i.e. colon, small intestine, etc), and whether certain natural defense mechanisms need to be passed through such as the blood-brain barrier, the transit time and delivery challenges can be greatly different (Yarin AL, 2010). Once drug an-ivies at its destination, it needs to be released at an appropriate rate for it to be effective. If the drug is released too rapidly it might not be completely absorbed, or it might cause gastro-intestinal irritation and other side effects. The drug delivery system must positively impact the rate of absorption, distribution, metabolism, and excretion of the drug or other substances in the body. In addition, the drug delivery system must allow the drug to bind to its target receptor and influence that receptor’s signaling and action, as well as other drugs, which might also be active in the body. Drug delivery systems also have severe restrictions on the materials and production processes that can be used. The drug delivery material must be compatible and bind easily with the drug, and be bioresorbable (i.e. degrade into fragments after use which are either metabolized or eliminated via normal excretory routes). The production process must respect stringent conditions on processing and chemistry that won’t degrade the drug, and still provide a cost effective product (Pathak A et al., 2008, Patel GM et al., 2010).

Figure 8. Nanorobots Drug Delivery

Role in Skin To cure skin diseases, a cream containing

nanorobots may be used. It could remove the right amount of dead skin, remove excess oils, add missing oils, apply the right amounts of natural moisturizing compounds, and even achieve the elusive goal of deep pore cleaning by actually reaching down into pores and cleaning them out. The cream could be a smart material with smooth-on, peel-off convenience. Cleaning Wounds

Nanorobots could help remove debris from wounds, decreasing the likelihood of infection. They would be particularly useful in cases of puncture wounds, where it might be difficult to treat using more conventional methods. In Diagnosis and Biopsy

Nanorobots assist in diagnosis and biopsy. They travel through bloodstream or tissues all over the body searching out infections, damaged organs, tumours, blocked blood vessels or cancer cells. When they locate any unwanted deposits or damaged organs, nanorobots take action to remove those deposits and repair damaged organs. Dental Applications

Nanorobots can be used for preventive/restorative &curative procedures. Dental nanorobots induce oral analgesia, desensitize teeth, manipulate the tissues to re-align and straighten malaligned teeth (orthodontic nanorobots). (Khosla R, 2009; Freitas Jr RA, 2000)

Figure 9. Nanorobotics in Dental Application

Maintenance of Oral Hygiene

A mouthwash full of smart nanomachines could identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem. Further, the devices would identify particles of food, plaque, or tartar, and lift them from teeth to be rinsed away. Being suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of toothbrush bristles or the fibres of floss. Subocclusally dwelling nanorobots delivered by dentifrice patrol all supra-gingival and sub-gingival surfaces metabolizing trapped organic matter performing continues calculus debridement.


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They prevent tooth decay and provide a continuous barrier to halitosis. As short-lifetime medical nanodevices, they could be built to last only a few minutes in the body before falling apart into materials of the sort found in foods (such as fibre). Cavity Preparation and Restoration

Multiple nanorobots working on the teeth in unison, invisible to the naked eye, may be used for cavity preparation and restoration of teeth. The cavity preparation is very precisely restricted to the de-mineralized enamel and dentin, thus providing maximum conservation of sound tooth structure. (Freitas Jr RA, 2000) Dentin Hyper Sensitivity

Dentin hyper sensitivity is a pathological phenomenon caused by pressure transmitted hydro dynamically to the pulp. Reconstructive dental nanorobots selectively and precisely occlude specific dentinal tubules within minutes, offering patients a quick and permanent cure from hypersensitivity (Schleyer TL, 2000) Esthetic Dentistry

They are used for dentition re-neutralization procedures in esthetic dentistry. They excavate old amalgam restorations and remanufacture teeth with biological materials, indistinguishable from original teeth (Schleyer TL, 2000) Tooth repair and repositioning

Nanodental techniques involve genetic engineering, tissue engineering, and tissue regeneration procedures for major tooth repair. Nanorobots provide complete dentition replacement therapy including both mineral and cellular components. Orthodontic nanorobots can directly manipulate the periodontal tissue, including gingival, periodontal ligament cementum and alveolar bone allowing rapid and pain less tooth straitening, rotation and vertical repositioning within minutes hours (Khosla R, 2009)

Figure 10. Nanorobots in Repositioning Tooth

Inducing Anesthesia

A colloidal suspension containing millions of active analgesic micron size dental nanorobots will be installed on

the patient’s gingiva. After contacting the surface of the crown or mucosa ,the ambulating nanorobots reach dentin by migrating into the gingival sulcus and pass painlessly through the lamina propria or through 1 to 3 microns thick layer of loose tissue at the CEJ. Upon reaching the dentin they enter the dentinal tubules up to 1to4 microns depth and proceed towards the pulp guided by a combination of chemical gradient, temperature differentials and positional navigation under nanocomputer control. Thus the migration of nanorobots from tooth surface to the pulp occurs in 100 sec. once installed in the pulp, they establish control over nerve impulse, and analgesic nanorobots commanded by the dentist shut down all sensitivity in any particular tooth requiring treatment. When the dentist presses the hand held control, the selected tooth is immediately anesthetized. After the procedure is completed the dentist orders the nanorobots to restore all sensation and egress from the tooth. Nanorobot analgesia offers great patient comfort, reduces anxiety, no needles, greater selectivity, controllability of analgesic effect; fasten completely reversible action; avoidance of side effects and complications. Role in Surgery

Nanorobots could also be programmed to perform delicate surgeries; such nanosurgeons could work at a level a thousand times more precise than the sharpest scalpel. By working on such a small scale, a nanorobot could operate without leaving the scars that conventional surgery does. Additionally, nanorobots could change your physical appearance. They could be programmed to perform cosmetic surgery, rearranging your atoms to change your ears, nose, eye color or any other physical feature you wish to alter. (Yarin AL, 2010). The use of nanorobots in surgery has provided additional tools for surgeons with unprecedented control over precision instruments, useful for minimally invasive surgery. Instead of manipulating surgical instruments, surgeons use joy stick handles to control robot arms containing miniature instruments to perform micro movements in cell surgery. A Surgical nanorobot, programmed by a human surgeon, could act as an autonomous on-site surgeon inside the human body. Various functions such as searching for pathology, diagnosis and removal or correction of the lesion by nanomanipulation can be performed and coordinated by an on-board computer (Li WJ et al., 2004). Helping the body clot

One particular kind of nanorobot is the clottocyte, or artificial platelet. The clottocyte carries a small mesh net that dissolves into a sticky membrane upon contact with blood plasma. Clotting could be up to 1,000 times faster than the body's natural clotting mechanism. Doctors could use clottocytes to treat hemophiliacs or patients with serious open wounds. (Yarin AL, 2010).


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Figure 11. Nanorobots in Body Clot

Parasite Removal

Nanorobots could wage micro-war on bacteria and small parasitic organisms inside a patient. It might take several nanorobots working together to destroy all the parasites.

Figure 12. Nanorobots Used In Blood Cell to Detect

Pathogens

Role in Diabetes

Medical nanorobots monitor diabetes by controlling nutrient concentrations in human body including blood glucose levels in diabetic patients. Patients with diabetes must take small blood samples many times a day to control glucose levels. Such procedures are uncomfortable and extremely inconvenient. Serious problems may affect the blood vessels if the correct target levels of glucose in the blood are not controlled appropriately. The level of sugar in the body can be observed via constant glucose monitoring using medical nanorobotics. This important data may help doctors and specialists to supervise and improve the patient medication and diary diet. Gout

Gout is a condition where the kidneys lose the ability to remove waste from the breakdown of fats from the bloodstream. This waste sometimes crystallizes at points near joints like the knees and ankles. People who suffer from gout experience intense pain at these joints. A nanorobot could break up the crystalline structures at the joints, providing relief from the symptoms, though it wouldn't be able to reverse the condition permanently.

Acting against Inflammatory Conditions An interesting utilization of nanorobots may be

their attachment to transmigrating inflammatory cells or white blood cells, to reach inflamed tissues and assist in their healing process. Thus they protect the body against harmful pathogens. In HIV

A similar approach like chemotherapy could be taken enable nanorobots to deliver Anti-HIV drugs. Such drug delivery nanorobots have been termed “pharmacytes”. In Chemotherapy

The most useful application of nanorobots in medicine was to identify cancer cells and destroy them. Nanorobots can be applied in chemotherapy to combat cancer through precise chemical dosage administration. Doctors hope to use nanorobots to treat cancer patients. The robots could either attack tumors directly using lasers, microwaves or ultrasonic signals or they could be part of a chemotherapy treatment, delivering medication directly to the cancer site. Doctors believe that by delivering small but precise doses of medication to the patient, side effects will be minimized without a loss in the medication's effectiveness (Wang J et al., 2011).

Figure 13. Nanorobots In Chemotherapy

Chromosome Replacement Theraphy

This Section describes a sequence of events likely to occur during a typical chromallocyte mission in which all cells in a specific organ inside the human body have their chromosomes replaced with new genetic material. In this procedure, the patient is scanned and prepped while a dose of personalized therapeutic chromallocytes is manufactured. After infusion into the patient, these mobile cell-repair nanorobots perform limited vascular surface travel into the capillary bed of the targeted tissue or organ. This is followed by extravasation, histonatation, cytopenetration, and complete chromatin replacement in the nucleus of the target cell, ending with a return to the bloodstream via the same route and subsequent extraction of the devices from the body at the original infusion site. (Wang J, 2009).


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Treating disorders in reproductive systems – Medical Nanorobot

Computer artwork of a medical nanorobot holding a sperm cell. Microscopic robot technology could be developed in the future to treat disorders, such as infertility, in new ways. This machine has identified a suitable sperm cell. (Mataric M, 1992)

Figure 13. Nanorobots Carrying Sperms

Nubots

Scientific field has given new type of robots to the world which are known as nubots.Nubot is the abbreviation of “nucleic Acid Robots”. These devices are operated at nanoscale and are highly beneficial for demonstrating the DNA test and blood cell detection. (Yarin AL, 2010; Li WJ et al., 2004)

CONCLUSION The approach presented in this paper, of combining a precise physical simulation to establish the environment in which nanorobots would inhabit, with a nanorobot control design simulator capable of modeling behavior and used for optimizing performance, has been shown to be of an extreme potential for exploration of techniques, strategies ,and nanorobot mobility considerations. The work is intended to serve as a practical framework for investigating designs and models of medical nanorobots, with an application to the case of establishing a trigger and control criteria for the treatment of stenosed blood vessels having been successfully demonstrated. Future work may include addition of a statistical and operational research envelope for evaluating large-scale performance, simulations of new environments and nanorobot designs. We strongly believe that the merging of the new technologies into operational nanomachines will go hand in hand with simulation ideality.

The authors report no conflicts of interest. The

authors alone are responsible for the content and writing of the paper.

ACKNOWLEDGEMENT

We thank Dr. Ravuri Venkataswamy, Chairman and Mr. R.V.Srinivas, Vice Chairman, Sri Venkateswara Group of Educational Institutions, R.V.S.Nagar, Chittoor, Andhra Pradesh, India for providing facilities to carry out this review work.

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nanobotics and their pharmaseutical aplications

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