Diabetes mellitus is one of the threatening, non-communicable and chronic ailments worldwide since ancient times to the current stage of human existence. The utilization of nanoparticles as a medicine in the treatment of diabetes is an attractive proposition. In the present study, herbal mediated cerium oxide nanoparticles (HMCeO2 NPs), herbal mediated silver nanoparticles (HMAg NPs) and Lawsonia intermix extract (LIE) was evaluated for them for in-vivo hypoglycemic effect and compared the potency. The resulting HMCeO2 NPs, HMAg NPs and Lawsonia inermis have been characterized by different analytical equipments such as X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Particle size analyzer (PSA), Field emission scanning electron microscope (FESEM) and High resolution transmission electron microscope (HRTEM). The synthesized NPs and Lawsonia inermis extract were assessed for toxicity by using acute oral toxicity using female albino mice (s) model by following OECD-425 guidelines. In in-vivo hypoglycemic animal model, the male wistar rats with weight varying between 180-200 gms were grouped as: normal control: did not receive any treatment, diabetic control (saline): received a single intraperitoneal dose of Streptozotocin (40 mg/kg), standard: received a single daily oral dose of 50 mg/kg body weight, HMCeO2 NPs: received single daily oral dose of 100 mg/kg, 200 mg/kg, HMAg NPs: received a single daily oral dose of 100 mg/kg, 200 mg/kg, and Lawsonia inermis: received a single daily oral dose of 100 mg/kg, 200 mg/kg. The herbal mediated NPs were considered safe as they have not shown toxic effects. From the current study results, it may conclude that, due to the advanced biological and pharmacological characters, the HMAg NPs depicted more potent hypoglycemic activity than that of LIE and CeO2 NPs.
A metal-inorganic composite, comprises of silver-molybdenum disulfide nanosheets (Ag@MoS2) was synthesized at low temperature. The Ag@MoS2 composite was drop-casted onto a glassy carbon electrode (GCE) for a highly selective dopamine (DA) detection in the presence of interfering compounds such as uric acid (UA) and ascorbic acid (AA). The physicochemical analysis of the nanosheets was carried out with X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. The as-prepared Ag@MoS2-modified GCE displayed excellent electrocatalytic activity toward DA oxidation, with a 0.2 μM detection limit at a signal-to-noise ratio of 3 and an extensive linear detection range from 1 μM to 500 μM (R2 = 0.9983). The fabricated non-enzymatic electrochemical sensor demonstrated superior selectivity and stability for the detection of DA with the removal of AA and UA interfering compounds.
Casein nanomicelles, a major fraction of milk protein, are emerging as a novel drug delivery system owing to their various structural and functional properties. Casein is further divided into α-, β- and κ-casein, and to date various models have been proposed to describe casein structure, but still no definite structure presenting a detailed assembly of the casein micelle has been found. Thus far, the submicellar model and Horne and Holt model are the most accepted models. This article presents a detailed review of casein micelles and their fractions, and the physicochemical properties that account for their numerous applications in nutraceutics, pharmaceutics and cosmetics. Due to their nanosize and self-assembling nature, casein nanomicelles are considered as excellent delivery carriers to provide better bioavailability and stability of various compounds such as vitamins, oils, polyphenols, fattyacids and minerals. Their amphiphilic nature also provides a great opportunity to deliver hydrophobic bioactives in various drug delivery systems such as nanoparticles, nanomicelles, nanogels and nanoemulsions to improve drug binding and targeting.
This paper focuses on the development of a drug delivery system for systemically controlled release of a poorly soluble drug, letrozole. The work meticulously describes the preparation and characterizations of 2-hydroxyethyl methacrylate (HEMA) polymerization onto hydrophilic acrylamide grafted low-density polyethylene (AAm-g-LDPE) surface for targeted drug release system. The surface morphology and thickness measurement of coated pHEMA layer were measured using scanning electron microscopy (SEM). The swelling study was done in deionized (DI) water and simulated uterine fluid (SUF, pH = 7.6). In vitro release of letrozole from the system was performed in SUF. Further, the release kinetics of letrozole from the system was studied using different mathematical models. The results, suggest that the rate of drug release can be altered by varying the concentrations of cross-linker in pHEMA. The optimized sample released 72% drug at the end of 72 h of measurement.
The antibacterial nature of graphene oxide (GO) has stimulated wide interest in the medical field. Although the antibacterial activity of GO towards bacteria has been well studied, a deeper understanding of the mechanism of action of GO is still lacking. The objective of the study was to elucidate the difference in the interactions of GO towards Gram-positive and Gram-negative bacteria. The synthesized GO was characterized by Ultraviolet-visible spectroscopy (UV-vis), Raman and Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Viability, time-kill and Lactose Dehydrogenase (LDH) release assays were carried out along with FESEM, TEM and ATR-FTIR analysis of GO treated bacterial cells. Characterizations of synthesized GO confirmed the transition of graphene to GO and the antibacterial activity of GO was concentration and time-dependent. Loss of membrane integrity in bacteria was enhanced with increasing GO concentrations and this corresponded to the elevated release of LDH in the reaction medium. Surface morphology of GO treated bacterial culture showed apparent differences in the mechanism of action of GO towards Gram-positive and Gram-negative bacteria where cell entrapment was mainly observed for Gram-positive Staphylococcus aureus and Enterococcus faecalis whereas membrane disruption due to physical contact was noted for Gram-negative Escherichia coli and Pseudomonas aeruginosa. ATR-FTIR characterizations of the GO treated bacterial cells showed changes in the fatty acids, amide I and amide II of proteins, peptides and amino acid regions compared to untreated bacterial cells. Therefore, the data generated further enhance our understanding of the antibacterial activity of GO towards bacteria.
Bio-nanogate involves synthesized or natural molecules as a 'gate' towards bioreceptors and responds upon the presence of targeted analytes in nanoscale dimension. Development of bio-nanogate improves analyte selectivity and signal response across various types of biosensors. The versatility of PAMAM dendrimers to form conjugates with guest molecules, such as proteins can be utilized in forming a bio-nanogate. PAMAM interaction with peptide bioreceptor for antibody detection is of interest in this study. This study investigated the interaction of synthesized immunogenic 'a' determinant (aD) region of hepatitis B virus surface antigen (HBsAg) with PAMAM G4 and anti-HBsAg antibody, as a potential bio-nanogate for anti-HBsAg detection. The aD peptide fused with maltose binding protein (MBP), was confirmed with Western blotting. Nano-Differential Scanning Fluorimetry (nano-DSF) study revealed that the interaction of MBP-aD with anti-HBsAg indicated a higher thermal stability as compared to its interaction with PAMAM G4. Electrochemical impedance spectroscopy showed that a higher binding constant of MBP-aD interaction with anti-HBsAg (0.92 μM-1) was observed at maximum saturation, as compared with PAMAM G4 (0.07 μM-1). Thermodynamic parameters demonstrated that MBP-aD interacted with anti-HBsAg and PAMAM G4, through van der Waals and hydrogen bonding. These analyses suggest that the weak interaction of MBP-aD and PAMAM G4 may form a potential bio-nanogate. It is hypothesized that the presence of anti-HBsAg has a higher affinity towards MBP-aD which may displace PAMAM G4 in the anti-HBsAg detection system. This interaction study is crucial as an initial platform of using peptide-PAMAM as a bio-nanogate in an antibody detection system.
Electrospinning is a common method to prepare nanofiber scaffolds for tissue engineering. One of the common cellulose esters, cellulose acetate butyrate (CAB), has been electrospun into nanofibers and studied. However, the intrinsic hydrophobicity of CAB limits its application in tissue engineering as it retards cell adhesion. In this study, the properties of CAB nanofibers were improved by fabricating the composite nanofibers made of CAB and hydrophilic polyethylene glycol (PEG). Different ratios of CAB to PEG were tested and only the ratio of 2:1 resulted in smooth and bead-free nanofibers. The tensile test results show that CAB/PEG composite nanofibers have 2-fold higher tensile strength than pure CAB nanofibers. The hydrophobicity of the composite nanofibers was also reduced based on the water contact angle analysis. As the hydrophilicity increases, the swelling ability of the composite nanofiber increases by 2-fold with more rapid biodegradation. The biocompatibility of the nanofibers was tested with normal human dermal fibroblasts (NHDF). The cell viability assay results revealed that the nanofibers are non-toxic. In addition to that, CAB/PEG nanofibers have better cell attachment compared to pure CAB nanofibers. Based on this study, CAB/PEG composite nanofibers could potentially be used as a nanofiber scaffold for applications in tissue engineering.
In this research, a milk thistle seed extract (MTSE)-rich medium was used as a capping and reducing agent for the one-pot biosynthesis of ZnO/Ag (5 wt%) nanostructure. The sample was systematically characterized through various techniques and its strong biomolecule‒metal interface structure was supported by the results. The efficacy of the derived nanostructure (MTSE/ZnO/Ag) was evaluated in vivo on the basis of its therapeutic effects on the main complications of Type 1 diabetes (hyperglycemia, hyperlipidemia, and insulin deficiency). For this purpose, the changes in the plasma values of fasting blood glucose, total cholesterol, total triglyceride, high-density lipoprotein cholesterol, and insulin in alloxan-diabetic Wistar male rats were compared with those in healthy and untreated diabetic controls after a treatment period of 16 days. The antidiabetic results of MTSE/ZnO/Ag were compared with those obtained from pristine ZnO, MTSE, and insulin therapies. The health conditions of the rats with Type 1 diabetes were significantly enhanced after treatment with MTSE/ZnO/Ag (p
In this present study, we have carried out the antioxidant function of transglutaminase (TG) identified from Arthrospira platensis (Ap) transcriptome. The antioxidant peptide ML11 (MLRSIGIPARL) has been predicted from the transglutaminase core domain and the peptide's free radical scavenging potential was evaluated and it shows that it functions on a dose dependent manner. The ML11 peptide cell toxicity was analysed in the human blood leucocytes which resulted no cytotoxic activity in any of the cell population. Moreover, the nanofibre mat encapsulated with antioxidant peptide ML11 was prepared by electrospinning technique. The antioxidant peptide ML11 encapsulated mat showed increase in fibre diameter compared to the chitosan polyvinyl alcohol blended mat. The change in the crystalline behaviour of both chitosan and polyvinyl alcohol polymer to the amorphous nature was determined by X-ray diffraction at the broad band between 20 and 30° (2θ°). FTIR revealed the functional groups which present in the polymer as well as the interaction between their components of chitosan (CS) and polyvinyl alcohol (PVA). The fibre retains the antioxidant activity due to the peptide encapsulated by scavenging the intracellular ROS that was confirmed by flowcytometry and fluorescence microscopy. The ML11 peptide encapsulated mat showed no cytotoxicity in the NIH-3T3 mouse embryonic fibroblast cells. Also, ML11 peptide encapsulated fibre showed potential wound healing activity in NIH-3T3 cells. Taken altogether, the study indicates that the wound healing potential of the ML11 peptide encapsulated nano fibre mat may be used as biopharmaceutical drug.
Carboxylesterases (CEs) are members of prominent esterase, and as their name imply, they catalyze the cleavage of ester linkages. By far, a considerable number of novel CEs have been identified to investigate their exquisite physiological and biochemical properties. They are abundant enzymes in nature, widely distributed in relatively broad temperature range and in various sources; both macroorganisms and microorganisms. Given the importance of these enzymes in broad industries, interest in the study of their mechanisms and structural-based engineering are greatly increasing. This review presents the current state of knowledge and understanding about the structure and functions of this ester-metabolizing enzyme, primarily from bacterial sources. In addition, the potential biotechnological applications of bacterial CEs are also encompassed. This review will be useful in understanding the molecular basis and structural protein of bacterial CEs that are significant for the advancement of enzymology field in industries.
This study developed a novel bioactive bone substitute (hydroxyapatite, HA) with improved anti-biofilm activity by functionalizing with curcumin (anti-biofilm compound) which provide sufficient flux of curcumin concentration for 14 days. The released curcumin acts to inhibit biofilm formation and control the number of viable planktonic cells simultaneously. To prepare curcumin-functionalized HA, different concentrations of curcumin (up to 3% w/v) were added simultaneously during the precipitation process of HA. The highest loading (50 mg/g HA) of curcumin onto HA was achieved with 2% w/v of curcumin. Physicochemical characterizations of curcumin-functionalized HA composites revealed that curcumin was successfully incorporated onto HA. Curcumin was sustainably released over 14 days, while higher curcumin release was observed in acidic condition (pH 4.4) compared to physiological (pH 7.4). The cytotoxicity assays revealed that no significant difference on bone cells growth on curcumin-functionalized HA and non-functionalized HA. Curcumin-functionalized HA was effective to inhibit bacterial cell attachment and subsequent biofilm maturation stages. The anti-biofilm effect was stronger against Staphylococcus aureus compared to Pseudomonas aeruginosa. The curcumin-functionalized HA composite significantly delayed the maturation of S. aureus compared to non-functionalized HA in which microcolonies of cells only begin to appear at 96 h. Up to 3.0 log reduction in colony forming unit (CFU)/mL of planktonic cells was noted at 24 h of incubation for both microorganisms. Thus, in this study we have suggested that curcumin loaded HA could be an alternative antimicrobial agent to control the risk of infections in post-surgical implants.
Oil-in-water (o/w) emulsion is utilized as an insecticide delivery system for mosquito control. However, evaporation inhibition adjuvant is needed to prevent fog drift, inhibit release of insecticidal actives and prolong suspension time. In the current study, we evaluated the effect of different short-chain alcohols, namely, propylene glycol, 1,3-propanediol, glycerol and crude glycerol, as adjuvants on the physicochemical properties of d-phenothrin o/w emulsion system. The bioactivity of optimized formulations containing 20 wt% glycerol (D1), 20 wt% propylene glycol (D2) and without added alcohol (negative control) were tested against larvae, pupae and adult Aedes aegypti (Ae. aegypti). It was found that propylene glycol produced smaller droplets at lower concentrations but poor long-term stability at higher concentrations, whereas glycerol had an appreciable effect on initial droplet size and stability with increasing concentration. According to the dose-response bioassays and room size chamber testing, the highest larvicidal, pupicidal and adulticidal activities were observed with D2, followed by D1 and negative control. Overall, the above study demonstrated improved emulsion stabilities and potency against Ae. aegypti larvae, pupae and adults using glycerol as adjuvant for effective mosquito control.
Natural enzymes possess several drawbacks which limits their application in industries, wastewater remediation and biomedical field. Therefore, in recent years researchers have developed enzyme mimicking nanomaterials and enzymatic hybrid nanoflower which are alternatives of enzyme. Nanozymes and organic inorganic hybrid nanoflower have been developed which mimics natural enzymes functionalities such as diverse enzyme mimicking activities, enhanced catalytic activities, low cost, ease of preparation, stability and biocompatibility. Nanozymes include metal and metal oxide nanoparticles mimicking oxidases, peroxidases, superoxide dismutase and catalases while enzymatic and non-enzymatic biomolecules were used for preparing hybrid nanoflower. In this review nanozymes and hybrid nanoflower have been compared in terms of physiochemical properties, common synthetic routes, mechanism of action, modification, green synthesis and application in the field of disease diagnosis, imaging, environmental remediation and disease treatment. We also address the current challenges facing nanozyme and hybrid nanoflower research and the possible way to fulfil their potential in future.
The novelty of this work is the conjugation of poly(ethylene) oxide (PEO) with the erbium oxide (Er2O3) nanoparticles using the electrospinning technique. In this work, synthesised PEO-coated Er2O3 nanofibres were characterised and evaluated for their cytotoxicity to assess their potential use as diagnostic nanofibres for magnetic resonance imaging (MRI). PEO has significantly impacted nanoparticle conductivity due to its lower ionic conductivity at room temperature. The findings showed that the surface roughness was improved over the nanofiller loading, implying an improvement in cell attachment. The release profile performed for drug-controlling purposes has demonstrated a stable release after 30 min. Cellular response in MCF-7 cells showed high biocompatibility of the synthesised nanofibres. The cytotoxicity assay results showed that the diagnostic nanofibres had excellent biocompatibility, indicating the feasibility for diagnosis purposes. With excellent contrast performance, the PEO-coated Er2O3 nanofibres developed novel T2 and T1-T2 dual-mode MRI diagnostic nanofibres leading to better cancer diagnosis. In conclusion, this work has demonstrated that the conjugation of PEO-coated Er2O3 nanofibres improved the surface modification of the Er2O3 nanoparticles as a potential diagnostic agent. Using PEO in this study as a carrier or polymer matrix significantly influenced the biocompatibility and internalisation efficiency of the Er2O3 nanoparticles without triggering any morphological changes after treatment. This work has suggested permissible concentrations of PEO-coated Er2O3 nanofibres for diagnostic uses.
Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.
Breast cancer is a global health concern that requires personalized therapies to prevent relapses, as conventional treatments may develop resistance over time. Photothermal therapy using spectral radiation or intense light emission is a broad-spectrum treatment that induces hyperthermia-mediated cancer cell death. MXene, a two-dimensional material, has been reported to have potential biological applications in photothermal therapy for cancer treatment. In this study, we investigated the apoptotic activity of MXene and UV-irradiated MXene in MCF-7 breast cancer cells by treating them with varying concentrations of MXene. The cytotoxicity of MXene and UV was evaluated by analyzing cellular morphology, nuclei condensation, caspase activation, and apoptotic cell death. We also assessed the effect of the combined treatment on the expression and cellular distribution of Tubulin, a key component of microtubules required for cell division. At low concentrations of MXene (up to 100 µg/ml), the level of cytotoxicity in MCF-7 cells was low. However, the combined treatment of MXene and UV resulted in a synergistic increase in cytotoxicity, causing rounded cellular morphology, condensed nuclei, caspase activation, and apoptotic cell death. Furthermore, the treatment reduced Tubulin protein expression and cellular distribution, indicating a potent inducer of cell death with potential application for cancer treatment. The study demonstrates that the combined treatment of MXene and UVB irradiation is a promising strategy for inducing apoptotic cell death in breast cancer cells, suggesting its potential as a therapeutic intervention for breast cancer.
In recent years, with increasing emphasis on healthy, green, and sustainable consumption concepts, plant-based foods have gained popularity among consumers. As widely sourced plant-based raw materials, legume proteins are considered sustainable and renewable alternatives to animal proteins. However, legume proteins have limited functional properties, which hinder their application in food products. LAB fermentation is a relatively natural processing method that is safer than chemical/physical modification methods and can enrich the functional properties of legume proteins through biodegradation and modification. Therefore, changes in legume protein composition, structure, and functional properties and their related mechanisms during LAB fermentation are described. In addition, the specific enzymatic hydrolysis mechanisms of different LAB proteolytic systems on legume proteins are also focused in this review. The unique proteolytic systems of different LAB induce specific enzymatic hydrolysis of legume proteins, resulting in the production of hydrolysates with diverse functional properties, including solubility, emulsibility, gelability, and foamability, which are determined by the composition (peptide/amino acid) and structure (secondary/tertiary) of legume proteins after LAB fermentation. The correlation between LAB-specific enzymatic hydrolysis, protein composition and structure, and protein functional properties will assist in selecting legume protein raw materials and LAB strains for legume plant-based food products and expand the application of legume proteins in the food industry.