Biogenically synthesized metal-based nanoparticles have emerged as an attractive alternative to traditional physicochemical methods. The conventional way to prepare metal nanoparticles involves using toxic chemicals as reducing agents and stabilizers, which is tedious to handle and highly detrimental to the environment. Hence, biological synthetic routes for the biosynthesis of metal nanoparticles have been widely explored in recent research. It involves using biological molecules present in organisms, such as bacteria, plants, and fungi, as well as vitamins and enzymes, to reduce, stabilize, and regulate nanoparticle growth. These green-synthesized nanoparticles have demonstrated promising biomedical applications, especially as antibacterial, anticancer, anti-inflammatory, and neuroprotective agents, owing to their superior biocompatibility and surface chemistry. In addition, there is potential to develop therapeutic formulations that leverage the interactions between nanoparticles’ properties and biological systems. This review discusses the mechanisms of biogenic synthetic routes, with a detailed discussion of plant, bacterial, enzymatic, fungal, and vitamin-mediated green synthetic metal-based nanoparticles and their applications in biomedical and drug delivery fields.

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side effects, creating a need for safer therapeutic alternatives. To address this, we developed a curcumin-loaded nanoemulsion (CUR-NE) using the spontaneous emulsification technique, aimed at enhancing the bioavailability and therapeutic efficacy of curcumin. The optimized nanoemulsion displayed a particle size of 76.42 nm, a zeta potential of −20.4 mV, and a high encapsulation efficiency of 93.69%, with a stable and uniform structure. The in vitro tests on SH-SY5Y neuroblastoma cells demonstrated that CUR-NE effectively protected against copper-induced toxicity, promoting significant cellular uptake. Pharmacokinetic studies revealed that CUR-NE exhibited a longer half-life and extended circulation time compared to free curcumin. Additionally, pharmacodynamic evaluations, including biochemical assays and histopathological analysis, confirmed that CUR-NE provided superior neuroprotection in copper overload conditions. These results emphasize the ability of CUR-NE to augment the therapeutic effects of curcumin, presenting a novel approach for managing copper-induced neurodegeneration. The study highlights the effectiveness of nanoemulsion-based delivery platforms in improving chelation treatments for neurological diseases.

Copper (Cu2+) dysregulation, often stemming from ATP7B gene mutations, exacerbates neurological disorders like Huntington’s, Alzheimer’s, and Parkinson's diseases. Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) shows promise in mitigating Cu2+ induced neurotoxicity by chelating intracellular Cu2+ ions, reducing oxidative stress, and restoring antioxidant enzyme function. However, challenges such as poor bioavailability hinder its therapeutic efficacy. Nano-delivery systems offer a solution by improving MiADMSA's solubility, stability, and targeted delivery, potentially minimizing off-target effects. In this study, MiADMSA was loaded into a polymer conjugated with lipoic acid (LA) and human serum albumin (HSA) using a coacervation crosslinking method. The prepared nanoparticles were optimized using a Box-Behnken design. Evaluation in SH-SY5Y cells revealed promising neuroprotective effects against Cu2+ induced neurotoxicity, highlighting the potential of MiADMSA-loaded nanocarriers as a therapeutic strategy for neurodegenerative diseases associated with metal dysregulation.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by β-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 series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited electric eel Acetylcholinesterase (AChE). The computational software Swiss ADME and molinspiration were used to unfold the probability of drug-likeness properties of the oximes derivatives. Substituted aromatic oximes with diethylamino or bromo group with free hydroxyl group ortho to oxime moiety were found efficient to regenerate the enzymatic activity in in-vitro AChE assay. The alkylation of the ortho hydroxyl group of derivatives led to the loss of reactivation potential. The derivatives with a hydroxyl group and without oxime group and vice versa did not show significant reactivation potency against tested OP toxicants. Further, we also evaluated the reactivation potential of these selected molecules on the rat brain homogenate against different OPs inhibited ChE and found maximum reactivation potency of oxime 2e. The in-vitro results were further validated by molecular docking and dynamic studies which showed that the hydroxyl group interacted with serine amino acids in the catalytic anionic site of AChE enzyme and was stable up to 200 ns consequently providing proper orientation to oxime moiety for reactivating the OP inhibited enzyme. It has thus been proved by the structure-activity relationship of oximes derivatives that hydroxyl group ortho to oxime is essential for reactivating OP inhibited electric eel AChE. Amongst the twenty-one oximes derivatives, 2e was found to be most active in regenerating the paraoxon, malaoxon, DCP and DCNP inhibited AChE enzyme.

INTRODUCTION:High incidence and fatality rates of cancer remain a global challenge. The success of conventional treatment modalities is being questioned on account of adverse effects. Photodynamic therapy (PDT) is a potential alternative. It utilizes a combination of photosensitizer (PS), light and oxygen to target the tissues locally, thereby minimizing the damage to neighboring healthy tissues. Conventional PSs suffer from poor selectivity, high hydrophobicity and sub-optimal yield of active radicals. Graphene nanomaterials (GNs) exhibit interesting particulate and photophysical properties in the context of their use in PDT. AREA COVERED:We focus on describing the mechanistic aspects of PDT-mediated elimination of cancer cells and the subsequent development of adaptive immunity. After covering up-to-date literature on the significant enhancement of PDT capability with GNs, we have discussed the probability of combining PDT with chemo-, immuno-, and photothermal therapy to make the treatment more effective. EXPERT OPINION:GNs can be synthesized in various size ranges, and their biocompatibility can be improved through surface functionalization and doping. These can be used as PS to generate ROS or conjugated with other PS molecules for treating deep-seated tumors. With increasing evidence on biosafety, such materials offer hope as antitumor therapeutics.

Multiple sclerosis (MS) is a neuroimmunological disorder which causes axonal damage, demyelination and paralysis. Although numerous therapeutics have been developed for the effective treatment of MS and a few have been approved in recent decades, complete remission and treatment of MS remain a matter of concern. Nanotechnology is a potential approach for manipulating the properties of materials at the molecular level to attain desired properties. This approach is effective in the treatment of several CNS disorders by enhancing drug delivery, bioavailability and efficacy. We have briefly discussed the neuroimmunological disorders with a particular emphasis on MS. We also explored nanoengineered drug delivery systems, describing several nano-formulations for the treatment of MS, challenges and future of nanotechnology.

Three-dimensional (3D)-printing, also known as additive manufacturing, has revolutionized various industries, including biomedical devices, by enabling the production of personalized implants tailored to individual patient anatomical variations. This review article provides an overview of the applications of 3D-Printed Medical Implants. By leveraging advanced imaging modalities and digital modeling software, clinicians can design and fabricate implants that ensure optimal fit, function, and biocompatibility for each patient. Additionally, 3D-printing has transformed cancer treatment as well as neurodegenerative disorders by facilitating the fabrication of patient-specific medical implants and devices used in surgical oncology, radiation therapy, and reconstructive surgery. These customized implants enhance treatment efficacy while minimizing adverse effects by precisely targeting cancerous tissues. Moreover, 3D-printing technology enables the development of 3D cell cultures, bridging the gap between traditional 2D cell cultures and in vivo models. This advancement enhances researchers' capabilities for studying cancer progression and evaluating responses to therapeutic interventions. Furthermore, 3D bioprinting shows promise as a therapeutic approach for neurological diseases, with preclinical studies demonstrating the efficacy of 3D-printed neural tissue scaffolds and implantable drug delivery platforms. Overall, 3D-printing holds significant potential in personalized medicine, offering innovative solutions to improve patient outcomes across various medical disciplines.

Neurological disorders (NDs) have a negative impact on the lives of individuals. There could be two explanations for this: unclear aetiology and lack of effective therapy. However, research in the past few years has revealed the role of bio-metals dyshomeostasis in NDs. The imbalance in copper (Cu) concentration may be one of the main causative factors in NDs. In this review, we have discussed the role of Cu in NDs, especially Alzheimer's disease (AD), including the molecular mechanisms involved in Cu-associated NDs like oxidative stress, neuroinflammation, and protein misfolding. We have also summarized the recent Cu-targeting approaches and highlighted the in vitro and in vivo studies recently being reported on the subject. Based on the earlier published reports, it could be speculated that the Cu targeting strategy might be an interesting and potential therapeutic approach for NDs. Various difficulties must be overcome to develop safe and efficient Cu-targeting medications for NDs.

The presence of arsenic in water bodies depends on pH, the redox condition of the solution, sorption, and exchange reactions. The World Health Organization (WHO) has established a guideline value of a maximum of 10 μg/L for arsenic in drinking water. Historically, arsenic has been used in fertilizers and medicines, and as a wood preservative; however, exposure to it over time may lead to skin diseases, impaired biochemical process, and various types of cancer. Bangladesh and West Bengal in India are the worst affected regions in terms of arsenic levels in water bodies and the magnitude of resultant health problems. In order to prevent arsenic pollution it is essential to understand the geochemical interactions of arsenic with its environment. The mechanism of arsenic release and mobility and its natural attenuation process are the key factors to elucidate the risk of arsenic contamination and to design and implement safe and effective treatment and remediation technologies.

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.

Fluoride (F) and arsenic (As) are two major contaminants of water and soil systems around the globe, causing potential toxicity to humans, plants, animals, and microbes. These contaminated soil systems can be restored by microorganisms that can tolerate toxic stress and provide rapid mineralization of soil, organic matter, and contaminants, using various tolerance mechanisms. Thus, the present study was undertaken with the arsenic hyper-tolerant bacterium Microbacterium paraoxydans strain IR-1 to determine its tolerance and toxicity to increasing doses of fluoride, either individually or in combination with arsenic, in terms of growth inhibition using a toxicity unit model. The minimum inhibitory concentration (MIC)and half maximal inhibitory concentration (IC50) values for fluoride increased, from 9 g/L to 11 g/L and from 5.91 ± 0.1 g/L to 6.32 ± 0.028 g/L, respectively, in the combination (F + As) group. The statistical comparison of observed and expected additive toxicities, with respect to toxicity unit (TU difference), using Student's t-test, was found to be highly significant (p < 0.001). This suggests the antagonistic effect of arsenic on fluoride toxicity to the strain IR-1. The unique stress tolerance of IR-1 ensures its survival as well as preponderance in fluoride and arsenic co-contaminated sites, thus paving the way for its possible application in the natural or artificial remediation of toxicant-exposed degraded soil systems.

Metalloids like arsenic (As) have been reported to be toxic to life since the existence of the very first organism on earth. It is a global pollutant which is widely distributed in all the domains of the earth whether it is soil, water, or air, and is highly toxic to all existing life forms. Arsenic was abundantly present in early oceans as evident by its high concentration in marine sediments. Therefore, early microorganisms were able to tolerate or resist even the high concentration of arsenic and exploit it as an energy source. The alarming rise in arsenic contamination is due to several geogenic sources such as weathering of rocks and volcanic eruptions, and anthropogenic activities including mining, smelting, and employing arsenic containing pesticides as shown in figure. The abundance of arsenic is apparent by the fact that it is a component of more than 200 minerals found in the earth's crust. 60% of these minerals have arsenate (As(V)) forms, 20% have sulfides and sulfosalts of arsenic, whereas remaining 20% have arsenites (As(III)), arsenides, silicates, and oxides of arsenic. It exists in several chemical forms which exert different toxicity. The inorganic forms especially arsenite is more toxic than methylated and organic arsenic species. The chemistry and speciation of arsenic in polluted domains are complex and perpetuated by several biotic and abiotic factors. Predominantly, the inorganic arsenic species (As(III), As(V)) are distributed in aquatic systems owing to their solubility over a wide pH range.

Hospital effluents are loaded with drugs, radioactive elements, pathogens, etc. Effluents from treatment plants at source sites may get mixed up with potable water, leading to numerous detrimental/toxic effects. In this study, efforts were made to investigate the toxic effects of one such effluent from a local hospital on the reproductive characteristics of mice when orally administered daily for 60 consecutive days. We primarily focused on the changes in the morphology of the sperm and its geometric morphometrics, i.e., sperm head length and width, area, and perimeter, measured using ImageJ software. The incidence of sperm defects was recorded, and variations in the morphometrics were analyzed by one-way ANOVA using Tukey's post hoc test. A physico-chemical characterization of the water samples was also performed to assess the basic water quality. In summary, the study revealed the critical role of treated water in inducing different abnormalities in sperm, such as the absence of a head, bent necks, abnormal neck attachment, highly coiled tails, and missing tails. Significant differences (p < 0.01 **, p < 0.001 ***) in the morphometrics of spermatozoa with banana heads, hammer heads, missing heads, pin heads, and missing hooks were noted compared to corresponding controls. It could thus be concluded that treated hospital effluent is still inadequately clean and contains significant amounts of toxicants that might be detrimental to sperm quality.

Medical treatment of arsenic toxicity is provided by chelating drugs, namely organic compounds capable of interacting with metal ions to form structures called “chelates.” Chelating agents are chemical compounds able to bind the metal with a higher affinity compared to endogenous ions and to form a hydrophilic complex that can be easily eliminated. This chapter summarizes the current status of chelation therapy with particular focus on the recent findings related to advantages/disadvantages of current chelators, the recent trend in finding a safe and specific antidote to treat cases of acute and chronic arsenic poisoning, and the future directions. The primary aim behind arsenic chelation is to reduce body arsenic burden by decreasing morbidity and preventing complications, which could be achieved to a greater extent by employing combination therapy, nanoparticle-based delivery to target sites, adjuvants, antioxidants, and herbal extracts.

Flavonoids belong to a class of natural, polyphenolic dietary compounds which modify the neuropathological state of the brain. Some flavonoids like quercetin and other, reduce the inflammation, carcinogenicity, and oxidation promotes neuroprotection and comprises the major component of cosmetics, medicinal and dietary supplements. Daily intake of flavonoids helps to mitigate the risk of several neurological disorders like Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, etc. Flavonoids exhibit their pharmacological effect through various mechanisms like cholinesterase inhibition, scavenging free radicals, memory enhancement via attenuation of amyloid plaques, tau targeting detoxification and neural antiinflammation. Administration of flavonoids to biological system has to pass through several biological checkpoints like first pass metabolism, intestinal absorption, and entry into blood brain barrier. Flavonoids exhibit difference in pharmacokinetic and pharmacodyanmic profile due to difference in their structures. Recent literature reports have proved promising therapeutic potential in neurological disorders. This chapter highlights the recent development of flavonoids prevailing in the field of neurodegenerative, its limitations and drug delivery approaches to encounter the challenges.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.

Background: Recent past decades have reported emerging of polymeric nanoparticles as a promising technique for controlled and targeted drug delivery. As nanocarriers, they have high drug loading and delivery to the specific site or targeted cells with an advantage of no drug leakage within en route and unloading of a drug in a sustained fashion at the site. These stimuli-responsive systems are functionalized in dendrimers, metallic nanoparticles, polymeric nanoparticles, liposomal nanoparticles, quantum dots. Purpose of Review: The authors reviewed the potential of smart stimuli-responsive carriers for therapeutic application and their behavior in external or internal stimuli like pH, temperature, redox, light, and magnet. These stimuli-responsive drug delivery systems behave differently in In vitro and In vivo drug release patterns. Stimuli-responsive nanosystems include both hydrophilic and hydrophobic systems. This review highlights the recent development of the physical properties and their application in specific drug delivery. Conclusion: The stimuli (smart, intelligent, programmed) drug delivery systems provide site-specific drug delivery with potential therapy for cancer, neurodegenerative, lifestyle disorders. As development and innovation, the stimuli-responsive based nanocarriers are moving at a fast pace and huge demand for biocompatible and biodegradable responsive polymers for effective and safe delivery.

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.