CD44 mediated colon cancer targeting mutlifaceted lignin nanoparticles: Synthesis, in vitro characterization and in vivo efficacy studies.

Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.

Wetland health assessment using DPSI framework: a case study in Kolkata Metropolitan Area.

Wetlands are among the most valuable components of the ecosystem, playing an important role in preventing floods, maintaining the hydrological cycle, protecting against natural hazards, and controlling local weather conditions and ecological restoration. The Kolkata Metropolitan Area (KMA) is considered one of the most ecologically valuable regions in terms of wetland ecosystem, but due to haphazard development and human activities, the wetlands of the city are under constant threat of degradation. Therefore, this study aims to assess the factors responsible for wetland health and their dynamics using Driving Force-Pressure-State-Impact (DPSI) framework. To assess wetland health during 2011-2020, seventeen indicators and four sub-indicators were selected to calculate weights using the analytic hierarchy process (AHP). The results showed that most of the municipalities in the healthy category were in the pressure (P) section in 2011, while fluctuations were observed in the impact (I) section in several wards during 2011-20. The condition section (S) showed the overall change in the water, vegetation, and built-up categories from 2011 to 2020, so the most dominant category was "healthy," followed by "unhealthy" and "poor." The highly significant factors worsening wetland health were population density (B1), road density (B3), per capita wastewater generation (B5), per capita solid waste generation (B7), biological oxygen demand (D1a), dissolved oxygen (D1b), pH (D1c), and total coliform (D1d). The results of the study can help develop sustainable conservation and management of the wetland ecosystem in the KMA urban area and at the global level with similar geographical conditions.

Monitoring built-up area expansion led by industrial transformation in Delhi using geospatial techniques.

Historically, industrialization has been a catalyst for built-up expansion generated by economic growth that transforms a landscape. In India, there is a paucity of exploration into how the economic shift transforms the cityscape. Therefore, the objective of current research work was to monitor built-up growth induced by industrialization using Landsat datasets and registered industry data. The k-means clustering technique was applied for assessing land use/land cover, Shannon entropy for sprawl, and Pearson for correlation between industrial growth and built-up expansion. The results manifest exponential trend in industrialization with 102-year registered industry record along with increase in built-up density from 0.30 in 1989 to 0.69 by 2019 and in the entire Delhi; it rose from 0.16 to 0.39. Furthermore, Shannon entropy confirmed the sprawl and the strong positive correlation was found among built-up of industrial areas and built-up of Delhi and registered industries. The striking chorological change in industrial as well as city's landscape was observed co-occurring with the dynamics of economic reforms. The outcome of current research could be utilized for the sustainable planning of industrial landscape in Delhi and cities with alike geographical conditions.

Understanding the Role of Free Radicals and Antioxidant Enzymes in Human Diseases.

Antioxidant enzymes being an integral part of the defense mechanism have a crucial role in cellular metabolism, essential for healthy growth and living of the cells. The main function is to scavenge and degrade the free radicals, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Endogenous antioxidant enzymes present in mitochondria, cytosol, and other cellular parts participate in capturing and repairing the oxidative damage to the system. Superoxide dismutase, catalase, and glutathione are antioxidant enzymes considered to be part of the first line of defense and are especially important in scavenging reactive oxygen species such as superoxide anion and hydrogen peroxide. Numerous studies in humans, as well as animal models, are correlated and reported about elevation in the enzymatic activity being involved in inhibiting oxidative damage and controlling the disease progression. Similarly, alterations due to enzymatic damage increase oxidative damage and have a key role in disease progression in diseases like cancer, atherosclerotic diseases, neurodegenerative diseases like Parkinson's, Alzheimer's, viral diseases, age-related ailments, etc. However, information about antioxidant enzymes, their specificity, free radicals involved in different diseases, and the oxidation process needs to be explored to a greater extent. This review focuses on our current understanding of the role of free radicals and the potential of various antioxidant enzymes, and their great scope in therapeutics against many dreadful diseases.

Recent Advancements in Lignin Valorization and Biomedical Applications: A Patent Review.

BACKGROUND: Synthetic polymers present disadvantages such as high cost, limited availability, safety concerns, environmental hazards and accumulation in body. Lignin, an aromatic biopolymer, is highly abundant and offers various advantages including cost-effectiveness, biocompatibility and biodegradability. It also possesses various pharmacological activities including antioxidant, antibacterial, anticancer and UV protection, thus lignin has become a popular biopolymer in recent years and is no more considered as bio-waste rather extensive research is been carried out on developing it as drug carrier. Lignin also has non-biomedical applications including dispersing agents, surfactants, detergent/ cleaning agents, energy storage, etc. Methods: This review compiles patents granted on production of technical lignin, different lignin therapeutic carriers and its biomedical and non-biomedical applications. The literature is collected from recent years including both articles as well as patents and is carefully analyzed and compiled in an easy to comprehend pattern for guiding future research. RESULTS: The reviewed patents and articles highlighted the advancement made in lignin isolation and valorization. Numerous lignin nanoformulations as drug delivery agents or as standalone entities with various pharmacological actions like antibacterial, antioxidant or UV protectant have been reported. As well as industrial applications of lignin as adhesives, insulators or supercapacitors have also made lignin a biopolymer of choice. CONCLUSION: Lignin being a bio-inspired polymer has huge potential in commercial applications. New methods of lignin isolation from lignocellulosic biomass including physical pretreatments, solvent fraction, and chemical and biological pretreatment have been widely patented. Several micro/nano lignin formulations with improved and controllable reactivity like nanocontainers, nanocapsules, nanoparticles have also been reported recently. Also, various pharmacological properties of lignin have also been explored, thus valorization of lignin is a hot topic of hour.

Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases.

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one's immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer's, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

Assessing the potential of lignin nanoparticles as drug carrier: Synthesis, cytotoxicity and genotoxicity studies.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.

Wood-Based Cellulose Nanofibrils: Haemocompatibility and Impact on the Development and Behaviour of Drosophila melanogaster.

Wood-based cellulose nanofibrils (CNF) offer an excellent scaffold for drug-delivery formulation development. However, toxicity and haemocompatibility of the drug carrier is always an important issue. In this study, toxicity-related issues of CNF were addressed. Different doses of CNF were orally administered to Drosophila and different tests like the developmental cycle, trypan blue exclusion assay, larva crawling assay, thermal sensitivity assay, cold sensitivity assay, larval light preference test, climbing behaviour, nitroblue tetrazolium (NBT) reduction assay, adult phenotype, and adult weight were conducted to observe the impact on its development and behaviour. A haemocompatibility assay was done on the blood taken from healthy Wistar rats. In Drosophila, the abnormalities in larval development and behaviour were observed in the behavioural assays. However, the cytotoxic effect could not be confirmed by the gut staining and level of reactive oxygen species. The larvae developed into an adult without any abnormality in the phenotype. The CNF did cause loss of weight in the adult flies and did not cause much toxicity within the body since there was no phenotypic defect. Hemolysis data also suggested that CNF was safe at lower doses, as the data was well within acceptable limits. All these results suggest that cellulose nanofibres have no significant cytotoxic effects on Drosophila. However, the developmental and behavioural abnormalities suggest that CNF may act as a behavioural teratogen.

Novel 4-in-1 strategy to combat colon cancer, drug resistance and cancer relapse utilizing functionalized bioinspiring lignin nanoparticle.

Colon cancer is one of the fatal forms of cancer all round the world with a equal frequency of occurrence in both male and female population. Mutational changes and defects in APC (Adenomatous Polyposis Coli) and DNA mismatch repair genes accompanied by genetic chaos in oncogenic pathways leads to colon cancer. Intensive study on pathogenesis of colon cancer has been made to decipher the mechanisms underlying the development and progress of the disease so as to develop effective treatment. However, a complete therapeutic regimen is still not available for combating this deadly disease. Hurdles faced by chemotherapy include drug resistance due to P-glycoprotein transporters, untoward effects on normal cells, high cost, bio-burden of the therapy, and the most dreadful drawback is cancer relapse. The concept of cancer relapse is related to development of oxidative stress that causes cell apoptosis. If the level of oxidative stress is inadequate to cause apoptosis then it leads to cell dormancy which may revive post chemotherapy. This hypothesis aims to put forward a combinatorial approach that includes utilizing a cost effective, biocompatible and environmentally benign nanoparticulate carrier made up of lignin, loaded with anti-cancer agent and P-gp modulator, and functionalized with ligand for CD44 receptors that are over expressed on cancer cells. Antioxidant effect of lignin will overcome dormancy of cancer cells making it possible for cell cycle specific drugs to kill them and prevent relapse and active targeting will prevent untoward effects on normal cells. Thus a robust and wholesome formulation can be developed to combat colon cancer.

Rutin restricts hydrogen peroxide-induced alterations by up-regulating the redox-system: An in vitro, in vivo and in silico study.

Rutin, a polyphenolic plant flavonoid, is found in citrus fruits, mulberry, cranberries and buckwheat with reported anti-diabetic, anti-fungal, anti-inflammatory and anti-bacterial activity. We appraise the effect of rutin on hydrogen peroxide (H2O2) mediated deregulation of antioxidant enzyme activity, non-enzymatic biomarkers, reactive oxygen species production (in vitro and in vivo) and on echinocyte formation (ex-vivo). In addition to it the interaction studies (in silico) against targeted enzymes and membrane proteins were also performed. A pre-treatment with rutin (16.3 µM) significantly attenuate the altered level of glutathione, sulfhydryl, malondialdehyde and carbonyl content. The activity and expression of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase were also decreased significantly (p < 0.01) in presence of H2O2, while pre-treatment of rutin ameliorates the effect of H2O2. Furthermore, rutin at higher tested concentration protects the morphology of erythrocytes by decreasing the reactive oxygen species level (p < 0.01) as compared to H2O2 treatment. In silico analysis with selected membrane proteins and enzymes revealed that the rutin did not modulate the structure and function of the preferred proteins. In addition, rutin down regulates the inducible nitric oxide synthase expression and up-regulate the nuclear factor (erythroid-related factor 2) expression. Moreover, the lower mean erythrocyte fragility values of rutin (0.53 ±â€¯0.024-0.61 ±â€¯0.014) alone or with H2O2 (0.65 ±â€¯0.021) indicate the protection and non-toxic behaviour. These finding suggests that rutin; a nutritional compound can reduce oxidative stress induced by H2O2 by increasing the expression of Nrf2 and endogenous antioxidant enzymes.

Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.

A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a, 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC50 values ranging between 0.95 and 47.96 µg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 µg/ml. Compounds 1g (IC50 value 0.76 µg/ml) and 1p (IC50 value 0.74 µg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g, 1p compared to standard acarbose.

Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application.

Interpenetrating polymer network (IPN) hydrogel microspheres of sodium carboxymethyl cellulose (NaCMC) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for oral controlled release delivery of a non-steroidal anti-inflammatory drug, diclofenac sodium (DS). The microspheres were prepared with various ratios of NaCMC to PVA, % drug loading and extent of crosslinking density at a fixed polymer weight. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acid and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results of this study suggest that DS loaded IPN microspheres were suitable for oral controlled release application.