Nanotechnology in the diagnostic and therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by ß-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD.

A review of FDA approved drugs and their formulations for the treatment of breast cancer.

Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs.

Surface plasmon resonance: A promising approach for label-free early cancer diagnosis.

Cancer is the second leading cause of death worldwide after cardiovascular disease. The major cause of high mortality is delayed detection. Therefore, detection at an early stage followed by early treatment can mitigate morbidity as well as mortality. The utilization of biomarker-based detection tools helps in early-stage recognition. Fortunately, biomarkers indicating disease status are released in to the circulation. These include traditional marker proteins as well as exosomes, micro-RNA (miRNA) and circulating tumor DNA (ct-DNA). Biosensors are biological and chemical reaction devices that generate signals based on analyte concentration. Due to analyte binding, these devices demonstrate high sensitivity and specificity. This review examines the use of surface plasmon resonance (SPR)-based sensors in the diagnosis of various cancer including those of the breast, prostate, lung, ovary, cervix and pancreas. SPR is a label-free, real-time and non-invasive optical biosensing technology representing a novel diagnostic tool in cancer detection.

MiADMSA abrogates sodium tungstate-induced oxidative stress in rats.

Tungsten (W) and its compounds have emerged as a relatively new area of environmental health concern in the last decade. Tungsten is environmentally benign due to its increasing use in armour-piercing munitions and as a replacement for lead in other ammunition. It has also been identified in various hazardous waste sites and therefore been proposed for inclusion in the Environmental Protection Agency National Priorities List. The major objective of this study was to evaluate the therapeutic efficacy of orally administered monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) against tungstate induced oxidative injury in blood, liver and kidneys of male Wistar rats. MiADMSA, a thiol chelator has gained wide recognition recently as a future chelating drug of choice specifically for arsenic and was chosen for this study as tungstate ions too have an affinity toward the -SH group thus, being less bioavailable in the body. We determined the effects of MiADMSA (50 mg/kg, p.o.) against sodium tungstate (500 ppm in drinking water, daily for 28 days) induced biochemical changes indicative of oxidative stress in blood, and other soft tissues of of male Wistar rats. Tungsten exposure led to an increased levels of Reactive Oxygen Species (ROS) in liver, kidney, spleen and blood accompanied also by an increase in TBARS levels. The GSH: GSSG ratio also showed a decrease on sodium tungstate intoxication. Treatment with MiADMSA restored most of the sodium tungstate-induced alterations in the biomarkers suggestive of oxidative stress. These preliminary results led us to conclude that sub-acute exposure to tungstate-induced oxidative stress could be effectively reduced by the administration of MiADMSA and thus might be a promising antidote for studying in detail its efficacy in reducing body tungstate burden and its excretion post tungstate exposure.

Organic-Molecule-Based Fluorescent Chemosensor for Nerve Agents and Organophosphorus Pesticides.

Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than biological weapons because of their ease of access. OP compounds are highly toxic compounds that cause irreversible inhibition of enzyme acetylcholinesterase, which is essential for hydrolysis of neurotransmitter acetylcholine, leading to series of neurological disorders and even death. Due to the extensive use of these organophosphorus compounds in agriculture, there is an increase in the environmental burden of these toxic chemicals, with severe environmental consequences. Hence, the rapid and sensitive, selective, real-time detection of OP compounds is very much required in terms of environmental protection, health, and survival. Several techniques have been developed over a few decades to easily detect them, but still, numerous challenges and problems remain to be solved. Major advancement has been observed in the development of sensors using the spectroscopic technique over recent years because of the advantages offered over other techniques, which we focus on in the presented review.

Nanodiamonds: A Versatile Drug-Delivery System in the Recent Therapeutics Scenario.

Nanodiamonds (ND) belong to the nano-carbon family, which involves several synthesis, post-synthesis methods, and other modifications for ND preparation. NDs have played vital role both inside and outside of medicine in recent years. The study of NDs has stated in early 1960s, NDs are smaller particles with a size of about 4-5 nm with confined size distribution, large-scale synthesis at lower costs relying on the carbon explosives ignition, apparent surface functional design along with bio-conjugation and extreme biocompatibility. It has been predicted that the ND's magnetic characteristics will contribute to the up-growth of various therapeutic promoters for delivery vehicles, diagnostic probes, gene therapy, tissue scaffolds, anti-bacterial and anti-viral treatments, and devices like nano-robots. Furthermore, the wide applications of biotechnology have displayed the potential usage of NDs in certain bioanalytical needs like fluorescent bio labeling through fluorescent and protein purification of proteins. In this current review, the determination of ND's design, property, classes, constancy, organization, surface modification, biocompatibility, and its applications in the biomedical field have penned. The usage of ND as anti-neoplastic agents and in other health related formulations have displayed exceptional results for future growth. Additionally, NDs provide other functionalities such as production of biodegradable surgical devices of bone, the assassination of drug resistant microbes and viruses, tissue engineering scaffolds, and aids in the delivery of genetic matter into the nucleus of cells.

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1ß, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.

Neurological Manifestations in COVID-19 Patients: A Meta-Analysis.

Common symptoms such as dizziness, headache, olfactory dysfunction, nausea, vomiting, etc. in COVID-19 patients have indicated the involvement of the nervous system. However, the exact association of the nervous system with COVID-19 infection is still unclear. Thus, we have conducted a meta-analysis of clinical studies associated with neurological problems in COVID-19 patients. We have searched for electronic databases with MeSH terms, and the studies for analysis were selected based on inclusion and exclusion criteria and quality assessment. The Stats Direct (version 3) was used for the analysis. The pooled prevalence with 95% confidence interval of various neurological manifestations reported in the COVID-19 patients was found to be headache 14.6% (12.2-17.2), fatigue 33.6% (29.5-37.8), olfactory dysfunction 26.4% (21.8-31.3), gustatory dysfunction 27.2% (22.3-32.3), vomiting 6.7% (5.5-8.0), nausea 9.8% (8.1-11.7), dizziness 6.7% (4.7-9.1), myalgia 21.4% (18.8-24.1), seizure 4.05% (2.5-5.8), cerebrovascular diseases 9.9% (6.8-13.4), sleep disorders 14.9% (1.9-36.8), altered mental status 17.1% (12.3-22.5), neuralgia 2.4% (0.8-4.7), arthralgia 19.9% (15.3-25.0), encephalopathy 23.5% (14.3-34.1), encephalitis 0.6% (0.2-1.3), malaise 38.3% (24.7-52.9), confusion 14.2% (6.9-23.5), movement disorders 5.2% (1.7-10.4), and Guillain-Barre syndrome 6.9% (2.3-13.7). However, the heterogeneity among studies was found to be high. Various neurological manifestations related to the central nervous system (CNS) and peripheral nervous system (PNS) are associated with COVID-19 patients.

Nanotechnological approaches for targeting amyloid-ß aggregation with potential for neurodegenerative disease therapy and diagnosis.

Neurodegenerative disorders can arise as a result of amyloid-ß production and misfolding of its protein. The complex anatomy of the brain and the unresolved mechanics of the central nervous system hinder drug delivery; the brain is sheathed in a highly protective blood-brain barrier, a tightly packed layer of endothelial cells that restrict the entry of certain substances into the brain. Nanotechnology has achieved success in delivery to the brain, with preclinical assessments showing an acceptable concentration of active drugs in the therapeutic range, and nanoparticles can be fabricated to inhibit amyloid and enhance the delivery of the therapeutic molecule. This review focuses on the interactions of nanoparticles with amyloid-ß aggregates and provides an assessment of their theranostic potential.

Box-Behnken Design Optimized TPGS Coated Bovine Serum Albumin Nanoparticles Loaded with Anastrozole.

PURPOSE: In this study, a novel D-α-tocopheryl polyethylene glycol succinate (TPGS) modified bovine serum albumin (BSA) nanoparticles (NPs) were developed for delivery of Anastrozole (ANZ) which is optimized by Box-Behnken design (BBD). Fabricated TPGS-ANZ-BSA NPs were evaluated for their physicochemical and drug release characteristics. METHODS: TPGS-ANZ-BSA NPs were prepared by desolvation thermal gelation method and the effects of critical process parameter (CPP) which are BSA amount, TPGS concentration and stirring speed on the critical quality attributes (CQA) such as % drug loading (%DL) and particle size were studied using BBD. TPGS-ANZ-BSA NPs were characterized using different spectroscopic techniques including UV-Visible and FTIR is used to confirm the entrapment of ANZ in BSA. DSC and PXRD revealed the amorphization of ANZ in the TPGS-ANZ-BSA NPs after freeze drying. Scanning electron microscopy (SEM) analysis was performed for the surface morphology analyses NPs. In vitro release studies were performed at pH 5.5 and pH 7.4 for 48h to mimic tumour microenvironment. RESULTS: The BBD optimized TPGS-ANZ-BSA NPs showed 107 nm particle size with %DL 8.5± 0.5%. The spectroscopic and thermal characterizations revealed the successful encapsulation of ANZ inside the NPs. The TPGS-ANZ-BSA NPs were found to exhibit burst release at pH 5.5 and sustained release at pH 7.4. The short-term stability displayed no significant changes in physical properties TPGS-ANZ-BSA NPs at room temperature for a period one month. CONCLUSION: The BBD optimized TPGS-ANZ-BSA nanoparticles showed enhanced physiochemical properties for ANZ and potential candidates for anticancer agent drugs delivery.

Interaction study of monoisoamyl dimercaptosuccinic acid with bovine serum albumin using biophysical and molecular docking approaches.

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 104 M-1 at 298 K. The value of thermodynamic parameters ΔG, ΔH, and ΔS described that the process is spontaneous, endothermic, and hydrophobic forces are involved in the interaction of MiADMSA with BSA. Competitive site marker experiments showed that MiADMSA binds to site-II of BSA. Conformational changes of BSA with the interaction of MiADMSA were apparent by CD, UV-Visible, FT-IR, and 3D fluorescence spectroscopy. To strengthen the experimental findings we have also performed a theoretical study on the BSA-MiADMSA complex. Two sites were identified with docking score of - 6.642 kcal/mol at site IIa and - 3.80 kcal/mol for site IIb via molecular docking study. Molecular dynamics simulation study inferred the stability of the BSA-MiADMSA complex which was analyzed in a long simulation run. The experimental and computational studies have shown the effective binding of MiADMSA with BSA which is essential for the transportation and elimination of a drug from the body.

Optimization of Surfactant- and Cosurfactant-Aided Pine Oil Nanoemulsions by Isothermal Low-Energy Methods for Anticholinesterase Activity.

Highly stable pine oil-loaded nanoemulsions were evaluated for nutraceutical and storage stability applications. Pine oil-loaded nanoemulsion preparation was done with pine oil as the oily phase and additionally with different ratios of the non-ionic surfactant (Tween 80) and cosurfactant (ethanol) in an aqueous solution using the isothermal low-energy or spontaneous emulsification method. A transparent and stable nanoemulsion was obtained with a combination of pine oil (5 wt %), surfactant mixture (35 wt %), and water quantity sufficient (qs) by the isothermal low-energy method. The mean droplet size and ζ-potential of the fabricated nanoemulsion were ≈14 nm and -3.4 mV, respectively. The size of the transparent nanoemulsion increased to ∼45 nm and showed turbidity at 60 °C. Microrheological investigation highlighted the gel-sol-gel conversion in the presence of applied angular frequency at 25 °C. The loss modulus shifted to lower frequency at 60 °C in comparison to other temperatures. The anticholinesterase (AChE) inhibition activity of the pine oil-loaded nanoemulsion suggested a possible therapeutic value, and at 0.10% concentration of the nanoemulsion, the AChE inhibition activity was ≈95.72 ± 5.59%. These studies have important implications in fabrication and optimization of a nanoemulsion as a delivery system for combating reminiscence in Alzheimer's disease and application in the nutraceutical-based industry. This isothermal low-energy method offers an advantage of preparing an edible oil delivery system using simple and rapid operational parameters.

Comparative efficacy of Nano and Bulk Monoisoamyl DMSA against arsenic-induced neurotoxicity in rats.

Chelation therapy is considered as a safe and effective strategy to combat metal poisoning. Arsenic is known to cause neurological dysfunctions such as impaired memory, encephalopathy, and peripheral neuropathy as it easily crosses the blood-brain barrier. Oxidative stress is one of the mechanisms suggested for arsenic-induced neurotoxicity. We prepared Solid Lipid nanoparticles loaded with Monoisoamyl 2, 3-dimercaptosuccinic acid (Nano-MiADMSA), and compared their efficacy with bulk MiADMSA for treating arsenic-induced neurological and other biochemical effects. Solid lipid nanoparticles entrapping MiADMSA were synthesized and particle characterization was carried out by transmission electron microscopy (TEM) and dynamic light scattering (DLS). An in vivo study was planned to investigate the therapeutic efficacy of MiADMSA-encapsulated solid lipid nanoparticles (Nano-MiADMSA; 50 mg/kg orally for 5 days) and compared it with bulk MiADMSA against sodium meta-arsenite exposed rats (25 ppm in drinking water, for 12 weeks) in male rats. The results suggested the size of Nano-MiADMSA was between 100-120 nm ranges. We noted enhanced chelating properties of Nano-MiADMSA compared with bulk MiADMSA as evident by the reversal of oxidative stress variables like blood δ-aminolevulinic acid dehydratase (δ-ALAD), Reactive Oxygen Species (ROS), Catalase activity, Superoxide Dismutase (SOD), Thiobarbituric Acid Reactive Substances (TBARS), Reduced Glutathione (GSH) and Oxidized Glutathione (GSSG), Glutathione Peroxidase (GPx), Glutathione-S-transferase (GST) and efficient removal of arsenic from the blood and tissues. Recoveries in neurobehavioral parameters further confirmed nano-MiADMSA to be more effective than bulk MiADMSA. We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes.

MiADMSA abrogates chronic copper-induced hepatic and immunological changes in Sprague Dawley rats.

Wilson disease (WD) is an autosomal-recessive disorder associated with the impaired copper metabolism, resulting in hepatic and neurologic manifestations. D-Pencillamine (DPA) is a first-line of treatment however, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), is gaining recognition recently as a future chelating agent of choice. We evaluated the effects of MiADMSA against copper-induced (20 mg/kg, orally, once, daily for 16 weeks) hepatic and immunological changes in the male Sprague Dawley (SD) rats. Copper overload increased the levels of pro-oxidant and concurrently decreased the levels of antioxidant enzymes in the liver. Increased oxidative stress triggered the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) in the liver and down-regulated the anti-inflammatory cytokine IL-4. Altered liver function parameters as well as serum immunoglobulins' (IgG, IgA, IgE, and IgM) levels, were also noted. MiADMSA treatment restored most of copper altered biochemical and immunological changes. Further, the histopathological changes proved that MiADMSA treatment ameliorated copper induced hepatic injury. Infra red spectra of liver tissue indicated shift in the characteristic -OH peak during copper exposure while the shifting came to normal in MiADMSA administered rat liver. We conclude that MiADMSA could be a promising antidote for the chronic copper toxicity and possibly in the clinical management of WD.

Monoisoamyl DMSA reduced copper-induced neurotoxicity by lowering 8-OHdG level, amyloid beta and Tau protein expressions in Sprague-Dawley rats.

INTRODUCTION: copper dyshomeostasis has long been linked with several neurodegenerative disorders. The binding of Cu with amyloid beta and other neuronal proteins in the brain leads to the generation of oxidative stress, which eventually causes neurotoxicity. METHOD: the present study was aimed at elucidating the efficacy of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) and d-penicillamine (DPA) (0.3 mEq kg-1, oral administration for 2 weeks) against Cu(ii)-induced (20 mg kg-1, oral administration for 16 weeks) neurotoxicity in Sprague-Dawley (SD) rats. RESULTS: we observed that the MiADMSA treatment modulated the altered oxidative and nitrosative stress parameters, antioxidant enzymes, and acetylcholinesterase (AChE) activity. Significant improvements were noticed in the neurobehavioral parameters except for the memory parameter. We also observed moderate improvement of memory impairment in the rats treated with MiADMSA and DPA post Cu(ii) exposure, as assessed by a passive avoidance test. Disease progression involves multiple factors and results in the up-regulation of intra and extracellular proteins such as amyloid beta and tau proteins; the expressions of these proteins were significantly reduced by the treatment proposed in our study, and these results were confirmed by ELISA and qRT-PCR. The expression of caspase-3 was higher in Cu(ii)-exposed rats, whereas it was lower in the MiADMSA-treated group. The proposed treatment reduced the copper-induced histological changes in the cortex and hippocampus regions of the brain. CONCLUSION: it can be summarised from the present study that MiADMSA is effective in reducing Cu(ii)-induced oxido-nitrosative stress, antioxidant defense enzymes, neurobehavioral changes, neuronal markers, apoptotic markers, and their genetic expressions. We conclude that chelation therapy using MiADMSA might be a promising approach for the treatment of copper-induced neurotoxicity.

MiADMSA ameliorate arsenic induced urinary bladder carcinogenesis in vivo and in vitro.

BACKGROUND AND PURPOSE: Arsenicosis is a major threat to public health and is a major cause of the development of urinary bladder cancer. Oxidative/ nitrosative stress is one of the key factors for these effects but the involvement of other associated factors is less known. There is a lack of data for the efficacy of chelator against urinary bladder carcinogenesis. The present study demonstrates the early signs of arsenic exposed urinary bladder carcinogenesis and its attenuation by Monoisoamyl dimercaptosuccinic acid (MiADMSA). METHODS: Male rats were exposed to 50 ppm of sodium arsenite and dimethylarsinic acid (DMA) via drinking water for 18 weeks and treated with MiADMSA (50 mg/kg, orally once daily for 5 days) for 3 weeks with a gap one week between the two courses of treatments. We compared in vivo data with in vitro by co-exposing 100 nM of sodium arsenite and DMA to rat (NBT-II) as well as human transitional epithelial carcinoma (T-24) cells with 100 nM of MiADMSA. RESULTS: The data showed that sodium arsenite and DMA exposure significantly increased the tissue arsenic contents, ROS, TBARS levels, catalase, SOD activities and significantly decreased GSH level which might be responsible for an increased 8-OHdG level. These changes might have increased pro-oncogenic biomarkers like MMP-9 and survivin in serum, bladder tissues, NBT-II, and T-24 cells. High cell migration and clonogenic potential in NBT-II and T-24 cells exposed to arsenic suggest pronounced carcinogenic potential. Significant recovery in these biomarkers was noted on treatment with MiADMSA. CONCLUSION: Early signs of urinary bladder carcinogenesis were observed in arsenic and DMA exposed rats which were linked to metal accumulation, oxidative/ nitrosative stress, 8-OHdG, MMP-9 and survivin which were reduced by MiADMSA possibly via its efficient chelation abilities in vivo and in vitro.

Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs.

Central nervous system (CNS) disorders especially neurodegenerative disorders are the major challenge for public health and demand the great attention of researchers to protect people against them. In past few decades, different treatment strategies have been adopted, but their therapeutic efficacy are not enough and have only shown partial mitigation of symptoms. Blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BSCFB) guard the CNS from harmful substances and pose as the major challenges in delivering drugs into CNS for treatment of CNS complications such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), stroke, epilepsy, brain tumors, multiple sclerosis (MS), and encephalitis, etc. Nanotechnology has come out as an exciting and promising new platform of treating neurological disorders and has shown great potential to overcome problems related to the conventional treatment approaches. Molecules can be nanoengineered to carry out multiple specific functions such as to cross the BBB, target specific cell or signaling pathway, respond to endogenous stimuli, and act as a vehicle for gene delivery, support nerve regeneration and cell survival. In present review, the role of nanocarrier systems such as liposomes, micelles, solid lipid nanoparticles (SLNPs), dendrimers, and nanoemulsions for delivery of various neurotherapeutic agents has been discussed, besides this, their mechanism of action, and nanoformulation of different neuroprotective agents like curcumin, edaravone, nerve growth factors in CNS disorders like Alzheimer's, Parkinsonism, epilepsy, stroke, and brain tumors has been reviewed.

Fluoride in Drinking Water and Skeletal Fluorosis: a Review of the Global Impact.

When safe and adequate exposure of an essential trace element is exceeded it becomes potentially toxic. Fluoride is one classic example of such a double edged sword which both plays a fundamental role in the normal growth and development of the body for example the consumption of levels between 0.5-1.0 ppm via drinking water is beneficial for prevention of dental caries but its excessive consumption leads to development of fluorosis. PURPOSE OF REVIEW: The abundance of fluorine in the environment as well as in drinking water sources are the major contributors to fluorosis. It is a serious public health concern as it is a noteworthy medical problem in 24 nations including India yet the threat of fluorosis has not been rooted out. The review focuses on recent findings related to skeletal fluorosis and role of oxidative stress in its development. The fluoride mitigation strategies adopted in recent years are also discussed. RECENT FINDINGS BASED ON CASE STUDIES: Recent findings revealed that consumption of fluoride at concentrations of 1.5 ppm is majorly responsible for skeletal fluorosis. The sampling from rural areas showed that 80% villages are having fluoride concentrations more than the WHO permissible limits and people residing in such areas are affected by the skeletal fluorosis and also in the regions of Africa and Asia endemic fluorosis have been accounted in the majority of the region affecting approximately 100 million people. Various mitigation programmes and strategies have been conducted all over the world using defluoridation. Fluorosis is a slow and progressive malady affecting our body and a serious concern to be taken into consideration and to be dealt with effectively. The fluoride toxicity although reversible, is a slow process and the side effects lack treatment options. The treatment options available are either not approachable or affordable in the rural areas commonly suffering from the fluoride toxicity. No specific treatments are available to date to treat skeletal fluorosis affectively; therefore, prevention is one of most safest and best approach to fight fluorosis. The current review lays emphasis on the skeletal fluorosis and its prevalence in recent years. It also includes the recent findings as well as the current strategies related to combat skeletal fluorosis and provides findings that might be helpful to promote the research in the field of effective treatment for fluorosis as well as development of easy and affordable methods of fluoride removal from water.

Gallic acid and MiADMSA reversed arsenic induced oxidative/nitrosative damage in rat red blood cells.

Arsenic (As) is naturally occurring toxic metalloid which is considered as a serious environmental and health concern. Red blood cells are the prime target for any toxicants as their population is higher in systemic circulation. High prevalence of anaemia too has been reported from arsenic contaminated area, suggesting possible linkage between arsenic and the damaging effects on RBCs. The exact mechanism for these effects is still not clear, however, oxidative/nitrosative stress might be one of the causative factors to play a key role. The present study was planned to evaluate the protective effects of a metal chelator, MiADMSA either alone or in combination with a natural antioxidant (gallic acid) for the reversal of arsenic induced oxidative damage in red blood cells. We collected rat RBCs and cultured them in appropriate medium. They were incubated with MiADMSA and gallic acid and then treated with sodium arsenite at 37 °C. Hemolysates were prepared and assayed for various biochemical parameters such as oxidative/nitrosative variables, osmotic fragility, acetylcholinesterase activity, and cellular metal accumulation. We found there was reversibility of oxidative/nitrosative stress variables, elevated cellular antioxidant power, and decreased osmotic fragility of red blood cells both in MiADMSA alone as well as in combination with gallic acid treated group compared with arsenic treated group. In conclusion, MiADMSA efficiently participated in the reversal of arsenic induced oxidative/nitrosative damage in red blood cells where as Gallic acid improved its reversal when given in combination with MiADMSA.

Design, synthesis, biological evaluation and molecular docking study of novel pyridoxine-triazoles as anti-Alzheimer's agents.

A series of multi-target natural product-pyridoxine based derivatives were designed, synthesized, characterized and evaluated as anti-Alzheimer agents. In vitro testing revealed the multi-functional properties of compounds such as inhibition of acetylcholinesterase (AChE), antioxidant and metal chelation. Among the series, 5i derivative was found most potent AChE inhibitor, possess antioxidant potential and chelating metal ions. Further binding interaction of 5i with AChE was studied using molecular docking, showed interaction with both PAS and CAS site of AChE. In silico predictions were also performed to predict toxicity and ADME properties of the molecule 5i and found within drug likeness range. Therefore, 5i could be a promising multi-functional compound that can be used for further development of novel drug for Alzheimer disease.