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Md. Mehdi Hasan et al. / International Journal of Biopharmaceutics. 2016; 7(2): e- ISSN Print ISSN International Journal of Biopharmaceutics Journal homepage: IJB NANOTECHNOLOGY DRUG DELIVERY SYSTEM: TOOLS IN ADVANCE PHARMACEUTICAL & HUMAN HEALTH CARE Md. Mehdi Hasan* 1, Farid Uddin 1, Md. Mohshin Islam 1, Mahbub Hasan 2, Kallol Banik 2, Md. Aminul Islam 1, Harun Ar Rashid 1 1 Department of Pharmacy, Faculty of Health science, Northern University Bangladesh, Dhaka -1205, Bangladesh. 2 Department of Pharmacy, Stamford University Bangladesh, Dhaka-1217, Bangladesh. ABSTRACT Nanotechnology ( nanotech ) is manipulation of matter on an atomic, molecular, and supramolecular scale. The earliest, widespread description of nanotechnology referred to the particular technological goal of precisely manipulating atoms and molecules for fabrication of macroscale products, also now referred to as molecular nanotechnology. A more generalized description of nanotechnology was subsequently established by the National Nanotechnology Initiative, which defines nanotechnology as the manipulation of matter with at least one dimension sized from 1 to 100 nanometers. Nanomedicine is the application of nanotechnology to medicine. Nanomedicine subsumes consists of three molecular technologies: nanoscale structured materials and devices; medical nanorobots; genomics, proteomics and artificial engineered microbes. It is also effective drug delivery system. Nanoparticles can be used in various purposes such as targeted drug delivery at the site of disease to improve the uptake of poorly soluble drugs, targeting of drugs to a specific site, and increasing the drug bioavailability. Physicochemical characteristics of nanoparticles and engineered nanomaterials including size, shape, chemical composition, physiochemical stability, crystal structure, surface area, surface energy, and surface roughness generally influence the toxic manifestations of these nanomaterials. The purpose of this review is to understand the advances of Nanotechnology in pharmaceutical & human health care. Key words: Nanotechnology, anesthesiology, diabetes mellitus, Detector, medicine,contact Lenses, microphysiometer, oral insulin. INTRODUCTION The history of nanotechnology traces the development of the concepts and experimental work falling under the broad category of nanotechnology. Although nanotechnology is a relatively recent development in scientific research, the development of its central concepts happened over a longer period of time. The emergence of nanotechnology in the 1980s was caused by the convergence of experimental advances Corresponding Author Md. Mehdi Hasan such as the invention of the scanning tunneling microscope in 1981 and the discovery of fullerenes in 1985, with the elucidation and popularization of a conceptual framework for the goals of nanotechnology beginning with the 1986 publication of the book Engines of Creation. The field was subject to growing public awareness and controversy in the early 2000s, with prominent debates about both its potential implications as well as the feasibility of the applications envisioned by advocates of molecular nanotechnology, and with governments moving to promote and fund research into nanotechnology. It remains to be seen to what extent nanotechnology will reshape medicine, but nano Md. Mehdi Hasan et al. / International Journal of Biopharmaceutics. 2016; 7(2): tech advances are continually being announced. A nanometer is one-billionth of a meter, too small to be seen with a conventional lab microscope. It is at this size scale about 100 nanometers or less that biological molecules and structures inside living cells operate. Nanoscience can be defined as study of phenomenon and manipulation of materials at atomic and molecular scales (Zäch M et al., 2006). Nanotechnology is related to design characterization, production and applications of structures, devices and systems by controlling shape and size at nanometer scale. Nanotechnology involves the creation and use of materials and devices at the level of molecules and atoms. Nanotechnology is the study, design, synthesis, creation, manipulation, and application of materials, devices, and systems at the nanometer scale (One meter consists of 1 billion nanometers). It is becoming increasingly important in fields like agriculture, engineering, construction, micro electronics and health care etc. The application of nanotechnology in the field of health care has become under great attention in recent times. There are many treatments today that take a lot of time and are also very expensive. Using nanotechnology, quicker and much cheaper treatments can be developed (Sahoo SK et al., 2007). Pharmaceutical nanotechnology embraces applications of nanoscience to pharmacy as nanomaterials, and as devices like drug delivery, diagnostic, imaging and biosensor (Daan JAC et al., 2010). Nanomedicine is defined as submicron size ( 1um) modules, used for treatment, diagnosis, monitoring, and control of biological system. Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve (Robert AF et al., 2005). There are two general ways to produce nanomaterials. The first is to start with a bulk material and then break it into smaller pieces using mechanical, chemical or other form of energy -- this is called top-down. Another way is to synthesize the material from atomic or molecular species via chemical reactions, allowing for the precursor particles to grow in size - this is called bottom-up (Lines MG., 2008). The increasing exposure of nanomaterials makes it imperative to assess the toxic effect of nanoparticle based materials; moreover, as the physical and chemical characteristics of nanomaterials influence the properties of nanoparticles, it is also more imperative to evaluate the physicochemical properties of nanomaterials including size, surface area, solubility, chemical composition, shape, agglomeration state, crystal structure, surface energy, surface charge, surface morphology, and surface coating and also role of individual characteristic property in imparting toxic manifestations. Reckoning with these facts, in this review, an attempt has been made to analyse the corelation of these physicochemical properties with the toxicity of engineered nanomaterials. NANOTECHNOLOGY IN MEDICINE: (Krešimir M et al., 2005) For centuries, man has searched for miracle cures to end suffering caused by disease and injury. Many researchers believe nanotechnology applications in medicine may be mankind s first 'giant step' toward this goal. According to Robert A. Freitas, nanomedicine is ... 1) the comprehensive monitoring, control, construction, repair, defense, and improvement of all human biological systems, working from the molecular level, using engineered nanodevices and nanostructures; 2) the science and technology of diagnosing, treating, and preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health, using molecular tools and molecular knowledge of the human body; 3) the employment of molecular machine systems to address medical problems, using molecular knowledge to maintain and improve human health at the molecular scale. One application of nanotechnology in medicine currently being developed involves employing nanoparticles to deliver drugs, heat, light or other substances to specific types of cells (such as cancer cells). Particles are engineered so that they are attracted to diseased cells, which allows direct treatment of those cells. This technique reduces damage to healthy cells in the body and allows for earlier detection of disease. For example, nanoparticles thatdeliver chemotherapy drugs directly to cancer cells are under development. Tests are in progress for targeted delivery of chemotherapy drugs and their final approval for their use with cancer patients is pending. Nanoscale structured materials are parts of nanomedicine with a rapid evolution, because of the impact of pharmaceutical industry. Pharmaceutical companies are trying today to develop targeted drug delivery using nanotechnology and drugs that already exist. The fact is that we do have useful drugs, but in some cases with pure bioavailability. For certain drugs that have non-concentration dependent pharmacodynamics, such as etalactam antibiotics, the clinical response is not associated with peak concentration, but rather with the duration of time over a critical therapeutic concentration (Hasan MM et al., 2016). The problem is how to deliver drugs right where we need it. The possibilities are great. For example, researchers are contemplating the possibility of using magnetic nanoparticles containing drugs to be delivered to specific parts of the body by means of magnetic field. Drugs can also be attached to nano- ligand, the role of which would be to deliver the drug only to target tissue while at the same time reducing its side effects. Methods available to improve dissolution include salt formation, micronization and addition of solvent or surface active agents( Rashid HA et al., 20 16). Some drugs have the problem of poor water solubility. The Nano systems Md. Mehdi Hasan et al. / International Journal of Biopharmaceutics. 2016; 7(2): company, which is part of the Elan Corporation, has developed a process called nanonization to solve this problem. First, drug crystals are reduced until they become particles of less than 400 nm in diameter. To stabilize the particles and prevent aggregation, a thin layer of polymeric surface modifiers is adsorbed onto crystal surfaces. The outcome is a suspension that functions like a solution, which can be used in various dosage forms, like pills, sprays or creams. Medical nanomaterials may also include smart drugs that become active only in specific circumstances. Yoshihisa Suzuki from Kyoto University has designed a novel drug molecule that releases antibiotic only in the presence of an infection. Suzuki bound the molecule of gentamicin to a hydrogel using a newly developed peptide linker. The linker can be cleaved by a proteinase enzyme produced by Pseudomonas aeruginosa. Tests on rats have shown that the antibiotic is not released if no Pseudomonas aeruginosabacteria are present. If any bacteria of this type are present, the enzyme produced by the microbes cleaves the linker and gentamicin is released to kill the bacteria. This is highly desirable because the indiscriminate prophylactic use of antibiotics is associated with the emergence of drug-resistant bacterial strains. Robert A. Freitas has designed an artificial red blood cell calledrespirocyte, a spherical nanorobot ofabout the bacterium size. This respirocyte, as represented in figure 1, would be made up of 18billion atoms, precisely arranged in a crystalline structure to form a miniature pressure tank. The tank would hold as many as nine billion oxygen andncarbon dioxide molecules. When respirocytes are injected into an individual s bloodstream, sensors onthe surface would detect oxygen and carbon dioxide levels in the blood. The sensors would then signal when it is time to load oxygen and unload carbondioxide, or vice versa. Respirocytes could store and transport 200 times more gas than red blood cells. Italso consists of glucose engine which will release glucose when there is deficiency in the body. Artificial engineered microbes are already being used to produce human hormones, for example. Human DNA is incorporated in the genome of the bacteria, which then start to produce human hormones, used to cure endocrine diseases. NANOMEDICINE IN ANESTHESIOLOGY: (Sarabjeet SS et al., 2007) Presently, an anaesthetist, while providing general anaesthesia (GA), induces the patient and maintains a certain level of anaesthesia by repeatedly assessing certain clinical parameters such as blood pressure and heart rate, or sometimes when sophisticated monitoring is not available, by lacrimation, colour of blood, etc. In today's world of rapid automation of almost every other thing, one can dream of automation of the above procedure. With nanotechnology, this dream can be realised in the future. Neuroelectronic interfacing, if successful, will allow nanodevices enabled electronic chips to be joined and linked to the human nervous system. More than million people in this world are undergoing surgery where anesthesia is essential. Currently an anesthesiologist is required to give the anesthesia and careful titration of the drugs is essential to prevent the side effects like hypotension, desaturation, preventing the intubation response. A situation in which use of, or exposure to, a violate product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote (Hasan MM et al., 2016 ). Advancement in the field of nanotechnology gives hope by applying in anesthesia by the use of nano robots. This gives excellent pain relief to million patients who undergo various types of surgery and also pain relief to ill cancer patients. In the design of nano robot there are two spaces: An interior space which will be a closed vacuum environment into which liquids from the outside cannot normally enter unless it is needed for chemical analysis. The exterior space will be subjected to various chemical liquids in our bodies. The nanorobots of typically0.5-3 microns in size with nm parts can freely flow inside the body exploring and detect the various receptors eg: GABA receptors in the brain, opioid receptors, neuromuscular junction receptors. It mainly consists of three main parts - the receptor sensor, central processing unit (CPU), effector and the power system. The purpose of receptor sensor is to identify the different anesthesia receptors on the cell. The effector is used to produce the post receptor event. The CPU controls all the activities. The power system provides the necessary energy for the working of the nanorobot. Nanotech Meets Contact Lenses and Virtual Reality: (Nanotech Breakthroughs, 2014) Nanotech could end up providing a solution to the need for bulky headsets in virtual reality environments, and theanswer involves contact lenses. Bellevue,WA based Innovega with its I Optik platform embedded a center filter and display lens at the center of a contact lens. The optical elements are smaller than the eye's pupil and therefore do not interfere with vision. A projector can hit those tiny optical elements, which guide images to the retina. But the retina is still getting the overall normal vision provided through the entire pupil, so the brain ends up viewing the projected images and the overall normal field of vision as one. The company says their ioptik platform provides wearers a 'virtual canvas' on which any media can be viewed or application run. The prototypes will feature up to six times the number of pixels and 46 times the screen size of mobile products that rely on designs limited by conventional optics. Those optics are said to deliver games, simulator environments, and movies that Md. Mehdi Hasan et al. / International Journal of Biopharmaceutics. 2016; 7(2): are truly immersive and mimic IMAX performance. The electronics are built in to a stylish pair of glasses without the bulk or weight of traditional approaches to video and VR eyewear. The setup can also display a multi-tasking dashboard that incorporates five or more typical screens, all while simultaneously providing the wearer a safe and clear view of their environment. The ioptik will be regulated in the United States as a Class II medical device, as normal contact lenses is rumored to be developing a medical device. A Nanotech Detector for Heart Attacks: (Nanotech Breakthroughs 2014) Nanosensors that detect heart attacks before they happen could save both lives and money. That is exactly what Eric Topol, MD, at San Diego based Scripps Health has been working on with Axel Scherer, PhD, of Caltech. Their technology involves tiny blood stream nanosensor chips that might sense the precursor of a heart attack. A person with such a tiny chip might get a warning on their smartphone or other wireless device that they should immediately see their cardiologist.the latest versions of the chip measure 90 microns much smaller than a grain of sand. A doctor or nurse might inject the nanosensor into a patient's arm, where it would flow down to the distal tip of the finger and embed itself, screening the blood for endothelial cells that are sloughed off an artery wall in a precursory period preceding a heart attack. The sensors are now being used for glucose detection in animal studies. Human trials should follow thereafter. The combination of a nanosensor and coupled smartphone could be used be used to track autoimmune disease and cancer. It could also be used to screen for rejection in patients with organ transplants. In this application, the nanosensor could be calibrated to detect the donor organ DNA in the blood, which would begin showing up in the blood as an early sign of rejection. Dragonfly-Inspired Black Silicon Fights Off Bacteria: (Nanotech Breakthroughs 2014) An array of antibiotic surfaces can be found in the natural world, inspiring scientists to develop manmade versions of them. A recent example of this trend can be found in research from Australian and Spanish scientists who have developed a nanomaterial out of black silicon with tiny spikes on its surface. The surface geometry of the material is similar to that of the wings of an Australian dragonfly known as the wandering percher, whose wings have tiny spikes that inhibit bacterial growth. In the lab, the scientists confirmed that the black silicon material proved to be effective against an array of Gram-negative and Grampositive bacteria as well as endospores. The researchers report that the breakthrough is the first physical bactericidal activity of [black silicon] or indeed for any hydrophilic surface. Tiny 3-D Printed Batteries: Researchers at Harvard University and the University of Illinois at Urbana-Champaign announced last year that they have figured out how to 3-D print miniature batteries about 1 mm across.the researchers, led by Jennifer A. Lewis, PhD, Harvard School of Engineering and Applied Sciences, created and tested materials, or inks, able to function as electrochemically active materials. The materials also had to harden into layers in just the right way so they could be stacked up in layers during the 3-D printing creating working anodes and cathodes.the recipe includes ink for the anode with nanoparticles of one lithium metal oxide compound, and an ink for the cathode from nanoparticles of another. The printer lays the ink onto the teeth of two gold combs to create a tightly interlaced stack of anodes and cathodes. The whole setup gets packaged into a tiny container and filled it with an electrolyte solution to complete the battery.tiny batteries could be gamechanging for the medical device industry, finding use in applications such as biomedical sensors and skin-based monitoring devices. In addition, they could be embedded into plastic housing of devices such as hearing aids.narayan says that he and his team are exploring the limits of 3-D printing. Using a 3-D printing technique known as two-photon polymerization, we have created small-scale medical devices such as drug delivery devices and biosensors. They have also developed a biocompatible riboflavin-containing photoinitiator for two-photon polymerization of tissue engineering scaffolds.two-photon polymerization uses lasers shining two different-wavelength beams on a sensitive material. Where the beams intersect, the material is polymerized. Then residual material can be washed out. Narayan continues, I think that more biocompatible materials for
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