Nanoparticles (NPs) are finding their application worldwide for specific kind of scientific research irrespective of their Fields such as chemical industries, biomedical, engineering, Material science, Environmental science, health care, cosmetics, food and feed, drug-gene delivery, environment and health. Nanoparticles are in a way into each and every aspect of our life mainly due to their small size which gives them large surface area to volume ratio and makes them distinct from those of bulk materials. Among several noble metal nanoparticles, silver and gold nanoparticles have attained a special focus along with Biodegradable and Magnetic nanoparticles. The Metallic nanoparticles are synthesized using chemical and Mechanical methods which are highly toxic and costly compared to biological system, hence there is a need to have a set of standard procedures that can be used to produce NPs in an environmentally safe and cost effective way. Thus green synthesis of NPs using biological systems like animal’s cells, plant extracts, Fungi, Bacteria are the latest ways to overcome Environmental problems and to make the overall process ecofriendly and cost effective. The plant based biological molecules provide a highly controlled assembly which makes them suitable for the metal nanoparticle synthesis. The huge plant diversity can be utilized for developing rapid and single step protocol with green principles over the conventional ones for the production of NPs.
The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, the antimicrobial property that is being majorly explored, though the anti-inflammatory property has its fair share of applications. Chitosan is effective materials for biomedical applications because of its biocompatibility, biodegradability and non-toxicity, apart from their antimicrobial activity and low immunogenicity, which clearly points to an immense potential for future development.
The Topic and present research work is ” Phytoextract Mediated Nanoparticle synthesis and their biomedical Applications ” in which, the concept of green synthesis of Nanoscale particles of biological polymer Chitosan and Silver Metal salt using plant leaf extract is being undertaken with further characterisation and evaluation of its biological potentials in treating global life threatening diseases.
In relevance to above aspect the brief information regarding
Nanoparticle Synthesis Method
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Is being introduced in this part.
Top to bottom and bottom to top approach of Nanoparticle synthesis
Synthesis of Nanoparticles basically uses two approaches; Top to bottom and bottom to top approach. Top to bottom approach uses Environmentally Toxic methods such as Mechanical / Ball milling, Chemical etching, Thermal / laser ablation and Sputtering. Bottom to top approach includes methods such as Chemical/Electrochemical, Precipitation, Vapour deposition, Atomic/Molecular Condensation, Sol gel process and Spray/Laser/Aerosol Pyrolysis which are also Environmentally Toxic methods and Biological/Green Synthesis using Bacteria/plant Extract/ Fungus are Non toxic Methods.
Plant Extract mediated nanoparticle synthesis
Biomolecules present in plant extracts are used to reduce metal ions to nanoparticles in a single-step green synthesis process. This biogenic reduction of metal ion to base metal is quite rapid, readily conducted at room temperature and pressure, and easily scaled up. Synthesis mediated by plant extracts is environmentally benign. The reducing agents involved include the various water soluble plant metabolites (e.g. alkaloids, phenolic compounds, terpenoids) and co-enzymes. Silver (Ag) nanoparticles have been the particular focus of plant-based synthesis.
Approach towards Neurodegenerative Disorders
Neurodegenerative processes are complex and involve many CNS tissue types, structures and biochemical processes. Factors believed involved in these processes are generation of Reactive Oxygen Species (ROS), associated inflammatory responses, pathological mechanisms responsible for the loss of dopaminergic neurons in PD, include elevated levels of iron, ubiquitin-proteasome system (UPS) dysfunction and impairment, altered calcium homeostasis, excitotoxicity and release of apoptotic factors along with the bio-molecular and genetic damage they produce. Since oxidative processes are essential to energy production, and to other biological functions, such as cell signaling, the process is not one of risk exposure, as for cigarettes and cancer, but one where normal physiological processes operate out of normal ranges and without adequate control Manton et al (2004).
Indian medicinal plants have been used for thousands of years in the traditional system of medicine (Ayurveda). Amongst these are plants used for the management of neurodegenerative diseases such as Parkinson’s, Alzheimer’s, loss of memory, degeneration of nerves and other neuronal disorders by the Ayurvedic practitioners. Though the causes of neurodegenerative diseases remain enigmatic, there is evidence, which indicates that defective energy metabolism, excitotoxicity and oxidative damage may be crucial factors (Beal et al 1995). The part of the Ayurvedic system that provides an approach to prevention and treatment of degenerative diseases is known as Rasayana, and plants used for this purpose are classed as rejuvenators. This group of plants generally possesses strong antioxidant activity but only a few have been investigated in detail (Auddy et al 2003)
The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF-alpha, Il-1beta, IFN-gamma), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase-3 and caspase-8, which are known effectors of apoptosis, has been reported in Parkinson’s disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson’s disease. (Hirsch et al 2003)
Parkinson’s disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent (Polymeropoulos at el 1997). The etiology of Parkinson’s disease is not known. Nevertheless a significant body of biochemical data from human brain autopsy studies and those from animal models point to an ongoing process of oxidative stress in the substantia nigra which could initiate dopaminergic neurodegeneration. It is not known whether oxidative stress is a primary or secondary event. Nevertheless, oxidative stress as induced by neurotoxins 6-hydroxydopamine and MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has been used in animal models to investigate the process of neurodegeneration with intend to develop antioxidant neuroprotective drugs. It is apparent that in these animal models radical scavengers, iron chelators, dopamine agonists, nitric oxide synthase inhibitors and certain calcium channel antagonists do induce neuroprotection against such toxins if given prior to the insult. Furthermore, recent work from human and animal studies has provided evidence for an inflammatory process. If an inflammatory response is involved in Parkinson’s disease it would be logical to consider antioxidants and the newly developed non-steroid anti-inflammatory drugs such as COX2 (cyclo-oxygenase) inhibitors as a form of treatment (GrÜnblatt at el 2000).
Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity. Overproduced free radicals react with cell membrane fatty acids and proteins impairing their function permanently. In addition, free radicals can lead to mutation and DNA damage that can be a predisposing factor for cancer and age-related disorders (Khansari at el 2009)
Alzheimer’s disease (AD) is a chronic neurological disorder characterized by memory impairment, cognitive dysfunction, behavioral disturbances, and deficits in activities of daily living. AD has been found to be associated with a cholinergic deficit in the post-mortem brain characterized by a significant decrease in acetylcholine amount. AD has become a major problem, particularly in developed countries due to increasing old-age population with a high life quality (Orhan at el 2004). Acetylcholine is a neurotransmitter inhibited primarily by acetylcholinesterase (AChE) and secondly by butyrylcholinesterase (BChE), considered to play a role in the pathology of AD (Hebert et al 1995). Both enzymes are present in the brain and are detected among neurofibrillary tangles and neuritic plaques (Beard et al., 1995). Despite the unknown etiology of AD, elevation of acetylcholine amount through AChE enzyme inhibition has been accepted as the most effective treatment strategy against AD (Arnold et al 1993).
Approach towards Anticancer treatment
According to WHO estimates for 2011, cancer now causes more deaths than all coronary heart disease or all stroke. The continuing global demographic and epidemiologic transitions signal an ever-increasing cancer burden over the next decades, particularly in low and middle income countries (LMIC), with over 20 million new cancer cases expected annually as early as 2025. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed worldwide. So far, the conventional therapeutic and surgical approaches to cancer therapy have not been able to curtail the rising incidence of cancers, worldwide. Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. The last decade has witnessed great research interest in biological activities of phenolic compounds that include anticancer, anti-oxidation and anti-inflammation among other things.
Disruption of execution of normal cell cycle plays a vital role in the development of cancer. Apoptosis or programmed cell death is a unique type of cell death observed in both physiological and pathological conditions. The hallmark features of apoptosis include both morphological and biochemical changes in the form of cell shrinkage, DNA fragmentation, membrane blebbings, chromatin condensation and loss of adhesion and rounding. Apoptosis yields numerous hints concerning efficient cancer chemotherapy, and many of the reported anticancer agents exert their effects by way of inducing apoptotic cell death. Most anticancer agents act by induction of apoptosis, cell cycle arrest, as well as an inhibition and proliferation of cell growth.
Considering this scenario and mode of interaction of therapeutic drugs a small attempt is made for evaluating the impact of plant mediated nanoscale polymer and salt particles on neurodegeneration and anticancer aspect.