Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Efficient sorption of As(III) from water by magnetite decorated porous carbon extracted from a biowaste material.

Arsenic is a highly toxic metal that causes cancer even at a low concentration and its removal from water resources is challenging. Herein, carbon extracted from waste onion bulbs is activated to cater for porosity and functionalized with magnetite (Fe3O4) nanoparticles (named MCK6) to address the challenge of As(III) removal. Synthesized MCK6 was highly mesoporous having a surface area of 208 m2/g, where magnetite nanoparticles (≤ 10 nm) are homogeneously distributed within a porous network. The developed adsorbent inherited functional groups from the biosource and magnetic property from magnetite making it ideal for removal of As(III). Further, MCK6 showed a maximum monolayer adsorption capacity (qm) of 10.2 mg/g at 298 K and pH 7. The adsorption thermodynamics delineates a non-spontaneous and endothermic reaction, where the kinetics followed pseudo 2nd order (R2 value of 0.977), while monolayer formation is explained by the Langmuir model. Moreover, MCK6 efficiently works to remove As(III) in a competitive metal ions system including Pb+2, Cd+2, and Ca+2, making it a suitable adsorbent to tackle contaminated water.

Improved photocatalytic decolorization of reactive black 5 dye through synthesis of graphene quantum dots-nitrogen-doped TiO2.

Graphene quantum dots (GQDs), a new solid-state electron transfer material was anchored to nitrogen-doped TiO2 via sol gel method. The introduction of GQDs effectively extended light absorption of TiO2 from UV to visible region. GQD-N-TiO2 demonstrated lower PL intensity at excitation wavelengths of 320 to 450 nm confirming enhanced exciton lifespan. GQD-N-TiO2-300 revealed higher surface area (191.91m2 g-1), pore diameter (1.94 nm), TEM particle size distribution (4.88 ± 1.26 nm) with lattice spacing of 0.45 nm and bandgap (2.91 eV). In addition, GQDs incorporation shifted XPS spectrum of Ti 2p to lower binding energy level (458.36 eV), while substitution of oxygen sites in TiO2 lattice by carbon were confirmed through deconvolution of C 1 s spectrum. Photocatalytic reaction followed the pseudo first order reaction and continuous reductions in apparent rate constant (Kapp) with incremental increase in RB5 concentration. Langmuir-Hinshelwood model showed surface reaction rate constants KC = 1.95 mg L-1 min-1 and KLH = 0.76 L mg-1. The active species trapping, and mechanism studies indicated the photocatalytic decolorization of RB5 through GQD-N-TiO2 was governed by type II heterojunction. Overall, the photodecolorization reactions were triggered by the formation of holes and reactive oxygen species. The presence of •OH, 1O2, and O2• during the photocatalytic process were confirmed through EPR analysis. The excellent photocatalytic decolorization of the synthesized nanocomposite against RB5 can be ascribed to the presence of GQDs in the TiO2 lattice that acted as excellent electron transporter and photosensitizer. This study provides a basis for using nonmetal, abundant, and benign materials like graphene quantum dots to enhance the TiO2 photocatalytic efficiency, opening new possibilities for environmental applications.

Bentonite binding with mercury(II) ion through promotion of reactive oxygen species derived from manure-based dissolved organic matter.

This study reports the mercury binding by bentonite clay influenced by cattle manure-derived dissolved organic matter (DOM). The DOM (as total organic carbon; TOC) was reacted with bentonite at 5.2 pH to monitor the subsequent uptake of Hg2+ for 5 days. The binding kinetics of Hg2+ to the resulting composite was studied (metal = 350 µM/L, pH 5.2). Bentonite-DOM bound much more Hg2+ than original bentonite and accredited to the establishment of further binding sites. On the other hand, the presence of DOM was found to decrease the Hg2+ binding on the clay surface, specifically, the percent decrease of metal with increasing DOM concentration. Post to binding of DOM with bentonite resulted in increased particle size diameter (~ 33.37- ~ 87.67 nm) by inducing the mineral modification of the pore size distribution, thus increasing the binding sites. The XPS and FTIR results confirm the pronounced physico-chemical features of bentonite-DOM more than that of bentonite. Hydroxyl and oxygen vacancies on the surface were found actively involved in Hg2+ uptake by bentonite-DOM composite. Furthermore, DOM increased the content of Hg2+ binding by ~ 10% (pseudo-second-order qe = 90.9-100.0) through boosting up Fe3+ reduction with the DOM. The quenching experiment revealed that more oxygen functionalities were generated in bentonite-DOM, where hydroxyl was found to be dominant specie for Hg2+ binding. The findings of this study can be used as theoretical reference for mineral metal interaction under inhibitory or facilitating role of DOM, risk assessment, management, and mobilization/immobilization of mercury in organic matter-containing environment.

Dynamic light scattering and zeta-potential as a tool for understanding the mechanism of pesticides binding toward individual components of transition metal nanoparticles and graphene oxide hybrids.

Pesticides present in their commercial formulations are studied for their preferable binding toward carbon-based graphene oxide (GO) or transition metal nanoparticles (Fe, Co, Ni, and Cu), present as hybrids. This simple study also reveals the mechanism of interaction of few selected different classes of pesticides, namely, λ-cyhalothrin, imidacloprid, and metsulfuron-methyl toward these hybrids. Individually, to study this comparative binding when hybrids are not used, the understanding of preferred binding toward any of these selected compounds could be challenging, costly, and time-consuming. Dynamic light scattering (DLS) is used to study the changes observed for hydrodynamic radius and zeta potential for the stability of the resulting products. This simple method can also be extended to identify the binding mechanism for other diverse set of combinations. These studies are supported by binding of GO with nanoparticles in batch adsorption and the best fit using Langmuir and Freundlich isotherms is presented. Moreover, pesticide adsorption toward GO-nanoparticle composites is also evidenced.

Isoxazole Derivatives against Carbonic Anhydrase: Synthesis, Molecular Docking, MD Simulations, and Free Energy Calculations Coupled with In Vitro Studies.

Heterocyclic compounds with a five-membered ring as a core, particularly those containing more than one heteroatom, have a wide spectrum of biological functions, especially in enzyme inhibition. In this study, we present the synthesis of five-membered heterocyclic isoxazole derivatives via sonication of ethyl butyrylacetate with aromatic aldehyde in the presence of a SnII-Mont K10 catalyst. The synthesized compounds were characterized using sophisticated spectroscopic methods. In vitro testing of the compounds reveals three derivatives with significant inhibitory action against carbonic anhydrase (CA) enzyme. The compound AC2 revealed the most promising inhibitory activity against CA among the entire series, with an IC50 = 112.3 ± 1.6 µM (%inh = 79.5) followed by AC3 with an IC50 = 228.4 ± 2.3 µM (%inh = 68.7) compared to the standard with 18.6 ± 0.5 µM (%inh = 87.0). Molecular docking (MD) study coupled with extensive MD simulations (400 ns) and MMPBSA study fully supported the in vitro enzyme inhibition results, evident from the computed ΔG bind (AC2 = -13.53 and AC3 = -12.49 kcal/mol). The in vitro and in silico studies are also augmented by a fluorescence-based enzymatic assay in which compounds AC2 and AC3 showed significant fluorescence enhancement. Therefore, on the basis of the present study, it is inferred that AC2 and AC3 may serve as a new framework for designing effective CA inhibitors.

PEGylated Protamine Letrozole Nanoparticles: A Promising Strategy to Combat Human Breast Cancer via MCF-7 Cell Lines.

The objective of the study was to develop PEGylated protamine letrozole nanoparticles to combat human breast cancer by modifying the release pattern of letrozole. Breast cancer is amongst the most prevalent diseases in women due to overactivity of human epidermal growth factor receptor 2 (HER2). PEG-protamine letrozole nanoparticle formulation was designed and optimized to alter the release pattern of the drug. The size, morphology, and structure of PEG-protamine letrozole NP were characterized by FTIR, XRD, Zetasizer, and SEM analysis. The result showed the PEG-protamine letrozole nanoparticles were irregular in shape and have size ranging from 258 nm to 388 nm, polydispersity index 0.114 to 0.45, zeta potential of 11.2 mV, and entrapment efficiency 89.93%. XRD studies have confirmed that the crystal structure of letrozole has become amorphous. The drug release study maintained the prolonged release for 72 hours. Moreover, the PEG-protamine letrozole NPs displayed a strong anticancer action compared to MCF-7 cells with an IC50 70 µM for letrozole and 50 µM for PEG-protamine letrozole NPs. Overall, our results indicate that letrozole PEG-protamine NPs alter the release profile of letrozole, which could be an excellent approach for overcoming letrozole resistance in human breast cancer.

Fluorescein based fluorescent and colorimetric sensors for sensitive detection of TNP explosive in aqueous medium: Application of logic gate.

Rapid detection of 2,4,6-trinitrophenol (TNP) in real samples has recently attained considerable attention from the perspective of national security, human health, and environmental safety. In this context, cost-effective and convenient detection of TNP explosive was accomplished through two new fluorescein based sensors F2 and F3. Sensors displayed effective fluorescence quenching response towards TNP in the aqueous medium. Highly sensitive fluorescence detection of TNP explosive (detection limit, 0.73 (F2) and 1.7 nM (F3)) was governed by ground-state charge transfer complex formation, facilitated by favorable H-bonding between sensor and TNP explosive. Fluorescence quenching mechanism for the detection of TNP explosive was investigated through UV-Visible absorption, dynamic light scattering (DLS), density functional theory (DFT) calculations, the Benesi-Hildebrand, and Job's plots. Advantageously, sensors displayed selective and immediate colorimetric recognition of TNP explosive. Importantly, sensors exhibited quick response time towards TNP even in the presence of potential interferences that make them highly suitable for practical applications. Sensors were successfully applied for fluorescent and colorimetric detection of TNP explosive in industrial water samples and fabrication of logic gates. Further, convenient contact mode and instant surface sensing of TNP explosive were achieved through the fabrication of fluorescent strips and explosive responsive test kits.

Synthesis and Tetraphenylethylene-Based Aggregation-Induced Emission Probe for Rapid Detection of Nitroaromatic Compounds in Aqueous Media.

Tetraphenylethylene (TPE) can be used to construct fluorescent probes with typical aggregation-induced emission (AIE) behavior for next-generation sensing applications. McMurry coupling and Suzuki cross coupling strategies provided the desired sensor thiophene-substituted tetraphenylethylene (THTPE). The synthesized TPE analogues were characterized by NMR spectroscopy and mass spectrometry. Maximum AIE of THTPE was observed in 90% water (H2O/THF) content due to extensive formation of aggregates. The AIE properties of THTPE have been utilized for facile detection of nitroaromatic compounds (NACs) (1.0 nM) through a fluorescence quenching mechanism. A paper strip adsorbed with the AIE-based THTPE fluorophore is developed for rapid and convenient detection of NAC-based analytes. Further, interaction of THTPE with analytes is also studied via Gaussian software at the DFT/B3LYP/6-31G(d) level of theory. Interaction energy, frontier molecular orbitals (FMOs), and non-covalent interaction (NCI) analyses are studied by using the same method. Computational results revealed that nitrobenzene (NB) has the strongest interaction while 1,3-dinitrobenzene (DNB) exhibits the least interaction with the sensor molecule. These computational results clearly demonstrate good agreement with experimental data.

Graphene quantum dot and iron co-doped TiO2 photocatalysts: Synthesis, performance evaluation and phytotoxicity studies.

The present study reports the synthesis, photocatalytic decolorization of reactive black 5 dye and phytotoxicity of graphene quantum dots (GQDs) and iron co-doped TiO2 photocatalysts via modified sol gel method. GQDs were synthesized by direct pyrolysis of citric acid (CA). Scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS), Raman spectroscopy, atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectroscopy (DRS), Brunauer-Emmett-Teller (BET) and photoluminescence spectroscopy (PL) were used to determine the physicochemical properties of the best performing photocatalysts. The results indicated improved physicochemical properties of GQD-0.1Fe-TiO2-300 with root mean square roughness (Rz) (33.82 nm), higher surface area (170.79 m2 g-1), pore volume (0.08 cm3 g-1), and bandgap (2.94 eV). Moreover, GQD-0.1Fe co-doping of TiO2 greatly improved the photocatalytic decolorization efficiency for RB5 dye. The photocatalytic reaction followed the pseudo first order reaction with gradual decrease in Kapp values for increment in RB5 concentration. The KC value was obtained as 2.45 mg L-1 min-1 while the KLH value was 0.45 L mg-1 indicating the heterogeneous reaction system followed the Langmuir-Hinshelwood isotherm and simultaneously occurring adsorption and photocatalytic processes. Photocatalytic reaction mechanism studies exhibited the holes and OH radicals as the main active species in the GQD-0.1Fe-TiO2-300 responsible for the decolorization of RB5. The proposed reaction pathway showed that both Fe-TiO2 and GQDs play important role in generation of electrons and holes. Additionally, GQD-0.1Fe-TiO2-300 were durable up to four cycles. Phytotoxicity assay displayed that treated water and best performing photocatalysts had no effect on Lycopersicon esculentum seed germination. Therefore, the proposed system can pave a viable solution for safe usage of dye loaded wastewater and effluent for irrigation after treatment.

Photocatalytic Decolorization and Biocidal Applications of Nonmetal Doped TiO2: Isotherm, Kinetic Modeling and In Silico Molecular Docking Studies.

Textile dyes and microbial contamination of surface water bodies have been recognized as emerging quality concerns around the globe. The simultaneous resolve of such impurities can pave the route for an amicable technological solution. This study reports the photocatalytic performance and the biocidal potential of nitrogen-doped TiO2 against reactive black 5 (RB5), a double azo dye and E. coli. Molecular docking was performed to identify and quantify the interactions of the TiO2 with ß-lactamase enzyme and to predict the biocidal mechanism. The sol-gel technique was employed for the synthesis of different mol% nitrogen-doped TiO2. The synthesized photocatalysts were characterized using thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET) and diffuse reflectance spectroscopy (DRS). The effects of different synthesis and reaction parameters were studied. RB5 dye degradation was monitored by tracking shifts in the absorption spectrum and percent chemical oxygen demand (COD) removal. The best nanomaterial depicted 5.57 nm crystallite size, 49.54 m2 g-1 specific surface area, 11-40 nm particle size with spherical morphologies, and uniform distribution. The RB5 decolorization data fits well with the pseudo-first-order kinetic model, and the maximum monolayer coverage capacity for the Langmuir adsorption model was found to be 40 mg g-1 with Kads of 0.113 mg-1. The LH model yielded a higher coefficient KC (1.15 mg L-1 h-1) compared to the adsorption constant KLH (0.3084 L mg-1). 90% COD removal was achieved in 60 min of irradiation, confirmed by the disappearance of spectral peaks. The best-optimized photocatalysts showed a noticeable biocidal potential against human pathogenic strain E. coli in 150 min. The biocidal mechanism of best-optimized photocatalyst was predicted by molecular docking simulation against E. coli ß-lactamase enzyme. The docking score (-7.6 kcal mol-1) and the binding interaction with the active site residues (Lys315, Thr316, and Glu272) of ß-lactamase further confirmed that inhibition of ß-lactamase could be a most probable mechanism of biocidal activity.

Phosphoric Acid Activated Carbon from Melia azedarach Waste Sawdust for Adsorptive Removal of Reactive Orange 16: Equilibrium Modelling and Thermodynamic Analysis.

Waste wood biomass as precursor for manufacturing activated carbon (AC) can provide a solution to ever increasing global water quality concerns. In our current work, Melia azedarach derived phosphoric acid-treated AC (MA-AC400) was manufactured at a laboratory scale. This novel MA-AC400 was tested for RO16 dye removal performance as a function of contact time, adsorbent dosage, pH, temperature and initial dye concentration in a batch scale arrangement. MA-AC400 was characterized via scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering (DLS) and fluorescence spectroscopy. MA-AC400 is characterized as mesoporous with BET surface area of 293.13 m2 g-1 and average pore width of 20.33 Å. pHPZC and Boehm titration confirm the acidic surface charges with dominance of phenolic functional groups. The average DLS particle size of MA-AC400 was found in the narrow range of 0.12 to 0.30 µm and this polydispersity was confirmed with multiple excitation fluorescence wavelengths. MA-AC400 showed equilibrium adsorption efficiency of 97.8% for RO16 dye at its initial concentration of 30 mg L-1 and adsorbent dose of 1 g L-1. Thermodynamic study endorsed the spontaneous, favorable, irreversible and exothermic process for RO16 adsorption onto MA-AC400. Equilibrium adsorption data was better explained by Langmuir with high goodness of fit (R2, 0.9964) and this fitness was endorsed with lower error functions. The kinetics data was found well fitted to pseudo-second order (PSO), and intra-particle diffusion kinetic models. Increasing diffusion constant values confirm the intraparticle diffusion at higher RO16 initial concentration and reverse was true for PSO chemisorption kinetics. MA-AC400 exhibited low desorption with studied eluents and its cost was calculated to be $8.36/kg.

Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs.

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a-3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a-3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ±â€¯0.43 to 273.43 ±â€¯0.96 µM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ±â€¯4.42 µM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a-4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b-4g exhibited a good inhibitory potential in the range of 43.86 ±â€¯1.11-163.43 ±â€¯2.03 µM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.

Synthesis and biological evaluation of novel oxadiazole derivatives: a new class of thymidine phosphorylase inhibitors as potential anti-tumor agents.

Based on the fact that the thymidine phosphorylase inhibitors are considered potential anti-tumor agents, a range of novel oxadiazole derivatives 3a-3u was designed and synthesized by a simple and facile synthetic route. The biological assay revealed that majority of compounds displayed modest inhibitory activity against thymidine phosphorylase at low micromolar concentrations (IC50 173.23±3.04 to 14.40±2.45µM). In the current study the most active compounds were 3h and 3q with IC50 values 14.40±2.45 and 17.60±1.07µM, respectively. Molecular docking studies were performed on the most active compounds (3h, 3k, 3o-3q) to show their binding mode.