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Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.

Graphene possesses wider biomedical applications including drug delivery, photothermal ablation of tumors, biosensors, and also in the disease diagnosis. The accidental or intentional exposure of the environment including plants, ecosystem, and humans toward graphene is gradually increasing. Therefore, graphene toxicity becomes a critical issue to be addressed despite their diverse applications in multiple fields. In this situation, the scientific community as well as the general public must get awareness about the toxicity of graphene. This article, therefore, reviews the investigations on graphene toxicity. This review reveals the toxicity of graphene in vitro, in vivo models along with the environmental toxicity. The advantages of graphene toxicity in bacterial cells and cancer cells were also reviewed.

Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC) induces 1% of all cancer deaths. Curcumin, the active constituent of turmeric is more effective in the treatment of various cancer. In the present study, with an aim to explore the mechanistic role of BDMC-A as a chemotherapeutic agent, we have investigated the inhibitory effect of BDMC-A on invasion, angiogenesis, and metastasis in Hep-2 cells and compared it with curcumin. Curcumin and BDMC-A treated Hep-2 cells were quantified using western blotting and RT-PCR technique to investigate the effect of Curcumin and BDMC-A on transcription factors involved in signal transduction cascade, invasion and angiogenesis associated markers. Pro-inflammatory markers of curcumin and BDMC-A treated Hep-2 cells were estimated using the ELISA kit. The results showed that BDMC-A might exhibit the anti-cancer activity by inhibiting transcription factors mainly NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ and β-catenin, which are responsible for tumor progression and malignancy. Downregulation of MMP-9, VEGF, IL-6 and IL-8 and upregulation of TIMP-2 levels further supports the anti-tumor potential of BDMC-A. Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.

As mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff's linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging.

PURPOSE: Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazo-benzamides are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel imidazo-benzamide derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. METHODS: The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. RESULTS: TBUEIB inhibited fifty precent A549 cells at a dose of 106 μM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. CONCLUSION: The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40199-021-00419-3.

Graphene possesses wider biomedical applications including drug delivery, photothermal ablation of tumors, biosensors, and also in the disease diagnosis. The accidental or intentional exposure of the environment including plants, ecosystem, and humans toward graphene is gradually increasing. Therefore, graphene toxicity becomes a critical issue to be addressed despite their diverse applications in multiple fields. In this situation, the scientific community as well as the general public must get awareness about the toxicity of graphene. This article, therefore, reviews the investigations on graphene toxicity. This review reveals the toxicity of graphene in vitro, in vivo models along with the environmental toxicity. The advantages of graphene toxicity in bacterial cells and cancer cells were also reviewed.

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.

Polymannose (PM) having a weight-average molar mass (Mw) of 30–53 kDa was synthesized by the polycondensation of mannose using phosphorous acid as the catalyst and characterized by various techniqu...

Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8 wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV-visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 μg/ml (equivalent to ~30 μg AmB) and showed hemolysis of5% at 200 μg/ml (equivalent to ~12 μg AmB) against human erythrocytes in vitro. In vitro release studies at 37 °C demonstrated steady release of AmB up to 20% from the conjugate with little burst effect in phosphate buffered saline whereas thrice the amount was released in human plasma in 72 h. AmBisome® used as a reference showed a very similar release profile in plasma. The conjugate exhibited potential anti-fungal activity against yeast strains such as C. albicans, C. neoformans and C. parapsilosis with the minimum inhibitory concentration (MIC) equivalent to AmB ranging from 0.7 to 1.1 μg/ml while AmBisome® and AmB alone showed the MIC between 0.78 and 1.5 and 0.53-0.78 μg/ml respectively. Although AmB has been conjugated to various natural and synthetic polymers to improve its solubility and reduce its toxicity, the results obtained in this study using the model protein BSA as a carrier point to the possibility of taking this pro-drug approach to human clinical use using human serum albumin (HSA) as the carrier, since HSA has emerged as a versatile drug carrier for treating diabetes and cancer and improving the pharmacokinetic profile of many drugs with US FDA approving HSA as a drug carrier for the anti-cancer drug paclitaxel (Abraxane®) for human use.

In immunocompromised patients, fungal infections are the major cause of morbidity and mortality. Currently, three major classes of drugs—polyenes, azoles, and echinocandins—with different mechanisms of action are used as antifungals for systemic infections. However, these conventional drugs were reported to induce toxic effects due to their low specificity, narrow spectrum of activity and drug–drug interactions. Some of these limitations could be overcome by altering the properties of existing drugs through physical and chemical modifications. For example, modification of amphotericin B (AmB), a polyene antibiotic includes the micellar suspension of AmB in deoxycholic acid (Fungizone®), non-covalent AmB lipid complexes (ABLC™), liposomal AmB (AmBisome®), and AmB colloidal dispersion (Amphocil™). All these formulations ensure the smoother release of AmB accompanied by its restricted distribution in the kidney, thereby lowering its nephrotoxicity. Although various methods such as polymeric micelles, nanoparticles and dendrimers were explored for enhancing the efficacy of the antifungal drugs, polymer–drug conjugates of antifungal drugs have received more attention in recent years. Polymer–drug conjugates improve the aqueous solubility of water-insoluble drugs, are stable in storage and reduce the toxicity of highly toxic drugs and are capable of releasing the drug at the site of action. This chapter discusses the polymer conjugates of antifungal drugs, their merits, and demerits. Studies reported so far show that the polymer–drug conjugates have significant advantages compared to conventional dosage forms for antifungal therapy.

In spite of the need for sensing bisdemethoxycurcumin analog (BDMCA), there is no detection system available so far. For the first time, we have demonstrated a sensing system for detecting BDMCA. Initially, chitosan thin films of three different molecular weights (low, average, high) were tested for the conductivity. The high molecular weight chitosan film was found to produce higher conductance and hence, used as the substrate. Addition of BDMCA to this substrate induced a significant conductance change (as revealed by impedance analyzer), making the detection system qualitative. Addition of increasing concentrations of BDMCA produced significantly concomitant increase in the conductivity (observed as decrease in current density as revealed by cyclic voltammetry) making the sensor quantitative. Our results show that this chitosan based electrochemical sensing system can be used for the rapid quantitative detection of BDMCA. As there is no BDMCA sensor available so far, this type of detection is very essential to monitor the pharmacokinetic behavior, the therapeutic dosage, bioavailability and related toxicity of BDMCA in different formulations and samples.

We have optimized a protocol for the preparation of bisdemethoxy curcumin analog nanoparticles (BDMCA-NP) by the solvent assisted process. The structural similarities between bulk and nano BDMCA were determined by Co-TLC, NMR and F-TIR. This shows that our synthesis protocol enhanced the dispersibility and reduce the size of BDMCA without altering the integrity of functional moieties and structure, which is crucial for anticancer and antioxidant activities. The morphology and size of BDMCA-NP as determined by SEM, HRTEM and DLS was found to be around 80 nm. BDMCA-NP treated breast cancer cell lines (MCF 7) showed cell death as characterized by MTT assay. Flow cytometric analysis of BDMCA-NP treated MCF 7 cell lines showed an increase of cell count in G2/M phase indicates the cell cycle arrest. Western blot analysis revealed the presence of caspase 3, caspase 9, cleaved fragments of PARP and Bax proteins in the BDMCA-NP treated MCF 7 cell lines, but not in untreated cell lines. To recap, we have prepared BDMCA-NP by solvent assisted process, which exerted anticancer activity against breast cancer cells, which may be due to (i) enhanced dispersibility and surface: volume ratio, (ii) apoptosis (iii) mitochondrial pathway induced cell death, (iv) G2/M phase cell cycle arrest and (v) disassembly of mitotic spindle of the cancer cells. Thus, nano BDMCA can be used as a potent anticancer agent.

Novel eco-friendly methods for the synthesis of metal nanoparticles are preferred and have recently been widely researched. In this study, a cost-effective and environmentally friendly method for the synthesis of gold nanoparticles was investigated. Costus pictus, also known as insulin plant due to its antidiabetic activity, was used as the reducing agent. Chloroaurate ions were rapidly reduced by the methanolic extract of Costus pictus, which was indicated by the color change from yellow to ruby red. The presence of a peak at 530 nm in UV-visible spectrophotometry confirmed the reduction of chloroaurate to gold nanoparticles. The reaction kinetics and effects of time, temperature, concentration of extract and substrate were also studied. The size and morphology of gold nanoparticles were analyzed using scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM) and they were found to be cuboidal, with a size of around 20 nm. The size of the particles was also analyzed by the particle size analyzer, and was found to be 45 nm. These particles were functionalized with bisdemethoxycurcumin analog (BDMCA). X-ray diffraction (XRD) analysis of prepared nanoparticles showed that the gold nanoparticles have a face centered cubic structure and that of functionalized nanoparticles showed peaks similar to that of BDMCA. Fourier transform infrared spectroscopy (FTIR) studies revealed the presence of reducing groups in the plant methanolic extract and the functionalization of nanoparticles with BDMCA was also confirmed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that, the BDMCA-functionalized gold nanocubes possess anticancer activity. The mechanism of action is discussed.

Intravenous route is the best strategy to accomplish fastest and highest delivery of drugs. Hydrophobic drugs like curcumin and its analog exhibit disadvantages like low bioavailability, poor absorption and rapid precipitation on intravenous delivery, all leading to its poor therapeutic value. These can be by-passed by enhancing the dispersity, stability and decreasing the size of the drug by nanotization. Thus, with an intention to deliver bis-demethoxy curcumin analog via intravenous route, we have studied the effect of DMSO, ethanol and acetone on the size, size distribution, stability and yield and identified the best solvent in terms of smallest size, narrow size distribution, more stability and high yield of nano bis-demethoxy curcumin analog (NBDMCA). NBDMCA prepared using DMSO showed the lowest mean particle size cum polydispersity index and highest zeta potential when compared to ethanol and acetone. Hence the DMSO based formulation can provide prolonged action and better efficacy at minimal doses. Thus, the DMSO based NBDMCA can emerge as an ideal therapeutic tool for human use.

The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz. , 20, 40, 60, 80, 100 μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5 μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo . We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

We have optimized a protocol for the preparation of bisdemethoxy curcumin analog nanoparticles (BDMCA-NP) by the solvent assisted process. The structural similarities between bulk and nano BDMCA were determined by Co-TLC, NMR and F-TIR. This shows that our synthesis protocol enhanced the dispersibility and reduce the size of BDMCA without altering the integrity of functional moieties and structure, which is crucial for anticancer and antioxidant activities. The morphology and size of BDMCA-NP as determined by SEM, HRTEM and DLS was found to be around 80 nm. BDMCA-NP treated breast cancer cell lines (MCF 7) showed cell death as characterized by MTT assay. Flow cytometric analysis of BDMCA-NP treated MCF 7 cell lines showed an increase of cell count in G2/M phase indicates the cell cycle arrest. Western blot analysis revealed the presence of caspase 3, caspase 9, cleaved fragments of PARP and Bax proteins in the BDMCA-NP treated MCF 7 cell lines, but not in untreated cell lines. To recap, we have prepared BDMCA-NP by solvent assisted process, which exerted anticancer activity against breast cancer cells, which may be due to (i) enhanced dispersibility and surface: volume ratio, (ii) apoptosis (iii) mitochondrial pathway induced cell death, (iv) G2/M phase cell cycle arrest and (v) disassembly of mitotic spindle of the cancer cells. Thus, nano BDMCA can be used as a potent anticancer agent.

The conventional drug delivery system has serious limitations such as lack of target specificity, altered effects and diminished potency. These limitations can be overcome by using biocompatible polymer as an effective drug delivery system. In this study, bis-demethoxy curcumin analog loaded Chitosan-starch (BDMCA-CS) nanocomposite particles were developed using different ratios of Chitosan and starch (3:1, 1:1 & 1:3) by ionic gelation method. The entrapment efficiency and drug loading capacity were found to be high for the formulation with the ratio 3:1 of BDMCA:CS. Physical characterization of the nanocomposite particles was determined using DLS and FTIR. The morphology of the BDMCA-CS nanocomposite particles were found to be spherical and regular by SEM analysis. In-vitro drug release profile of the BDMCA-CS nanocomposite particles showed a very slow and sustained diffusion controlled release of the drug. The cancer cells targeting ability of the BDMCA-CS nanocomposite particles were confirmed by performing MTT assay on MCF-7 breast cancer cell lines and VERO cell lines.

We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-?) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-? and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure. � 2015 The Authors.