Formation of Gold Nanoparticles in Water-in-Oil Microemulsions: Experiment, Mechanism, and Simulation.

Self-assembled water-in-oil (W/O) microemulsions have been reported as a suitable route for synthesis of size-controlled nanoparticles. However, the mechanism of formation of nanoparticles in microemulsions is still not completely understood. In this work, gold nanoparticles (GNPs) were synthesized via the W/O microemulsion route. As the molar ratio of water and dioctyl sodium sulphosuccinate (AOT) (R) increased from 2.5 to 5.0 to 7.5, the corresponding water drop diameter increased from 2.7 to 5.0 to 7.3 nm. In parallel, the mean hydrodynamic diameter of GNPs increased from 6.5 to 11.3 to 15.6 nm for corresponding R values of 2.5, 5.0, and 7.5. Therefore, although there is a monotonically increasing trend of the mean diameter of GNPs with the initial drop diameter, for all values of R, the mean diameter of GNPs was significantly higher than the initial drop diameter. Consequently, previously known simulation vastly underpredicts the experimental GNP diameter. However, only on redefining the particle-particle coagulation event (during coalescence of microemulsion drops containing particles) does the current kinetic Monte Carlo (kMC) simulation agree well with the experimental results. In addition, we also find that the coagulation efficiency of solid nanoparticles (ßp) increases with R, and ßp is lesser than the coalescence efficiency of liquid drops (ßd) over the range of R values concerned. Hence, a combined simulation and experimental study enumerates the dynamics of size evolution of nanoparticles and the events involved in their formation in a W/O microemulsion system.

Engineered polyethersulfone membrane for well-dispersed silver nanoparticle impregnation at high loading: high water permeate flux and biofouling prevention.

We present a new method for impregnation of silver nanoparticles (Ag NPs) at high loading on polyethersulfone (PES) membrane's external surface, simultaneously retaining native membrane's porosity - to achieve a high water permeate flux without biofouling. This was possible by PES membrane's surface modification with acrylic acid (AA), finally leading to AA-Ag-PES membrane. AA-Ag-PES had a high (9.04%) Ag-NP loading selectively on membrane surface, as discrete, smaller (mean size: 20 nm) nanoparticles (NPs). In nonfunctionalized Ag-PES, aggregated (mean size: 70 nm) NPs, with lower Ag loading (0.73 wt.%) was obtained, with NP being present both on membrane surface and inside pores. Consequently, AA-Ag-PES could maintain similar water permeability and porosity (10,153.05 Lm-2 h-1bar-1 and 69.98%, respectively), as in native PES (11,368.74 Lm-2 h-1bar-1 and 68.86%, respectively); whereas both parameters dropped significantly for Ag-PES (4,869.66 Lm-2 h-1bar-1 and 49.02%, respectively). AA-Ag-PES also showed least flux reduction (7.7%) due to its anti-biofouling property and high flux recovery after usage and cleaning, compared to native PES and Ag-PES membrane's much higher flux reduction (54.29% and 36.7%, respectively). Hence, discrete NP impregnation, avoiding pore blockage, is key for achieving high water flux and anti-biofouling properties (in AA-Ag-PES), compared to non-functionalized Ag-PES, due to aggregated Ag-NPs inside its pores.

Design of Ultrasensitive Protein Biosensor Strips for Selective Detection of Aromatic Contaminants in Environmental Wastewater.

Phenol and its derivatives constitute a class of highly toxic xenobiotics that pollute both river and groundwater. Here, we use a highly stable enzyme-based in vitro biosensing scaffold to develop a chip-based environmental diagnostic for in situ accurate, direct detection of phenol with selectively down to 10 ppb. Mesoporous silica nanoparticles (MCM41) having a pore diameter of 6.5 nm was screened and found to be the optimal solid support for creation of a robust immobilized protein based sensor, which retains stability, enzyme activity, sensitivity, and selectivity at par with solution format. The sensor strip exhibits minimal cross reactivity in simulated wastewater, crowded with several common pollutants. Moreover, this design is competent towards detection of phenol content with 95% accuracy in real-time environmental samples collected from local surroundings, making it a viable candidate for commercialization. The enzyme has been further modified via evolution driven mutagenesis to generate an exclusive 2,3-dimethylphenol sensor with equivalent selectivity and sensitivity as the native phenol sensor. Thus, this approach can be extended to generate a battery of sensors for other priority aromatic pollutants, highlighting the versatility of the biosensor unit. This novel biosensor design presents promising potential for direct detection and can be integrated in a device format for on-site pollutant monitoring.

Impact of density of coating agent on antibacterial activity of silver nanoparticle impregnated plasma treated activated carbon.

To use stabilized nanoparticles (NPs) in water as disinfectants over a very long period, the amount of coating agent (for NP stabilization) needs to be optimized. To this end, silver nanoparticles (Ag-NPs) with two different coating densities of tri-sodium citrate (12.05 and 46.17molecules/nm2, respectively), yet of very similar particle size (29 and 27 nm, respectively) were synthesized. Both sets of citrate capped NPs were then separately impregnated on plasma treated activated carbon (AC), with similar Ag loading of 0.8 and 0.82wt.%, respectively. On passing contaminated water (containing 104 CFU Escherichia coli/mL of water) through a continuous flow-column packed with Ag/AC, zero cell concentration was achieved in 22 and 39 min, with Ag-NPs (impregnated on AC, named as Ag/AC) having lower and higher coating density, respectively. Therefore, even on ensuring similar Ag-NP size and loading, there is a significant difference in antibacterial performance based on citrate coating density in Ag/AC. This is observed in lower coating density case, due to both: (i) higher Ag+ ion release from Ag-NP and (ii) stronger binding of individual Ag-NPs on AC. The latter ensures that, Ag-NP does not detach from the AC surface for a long duration. TGA-DSC shows that Ag-NPs with a low coating density bind to AC with 4.55 times higher adsorption energy, compared to Ag/AC with a high coating density, implying stronger binding. Therefore, coating density is an important parameter for achieving higher antibacterial efficacy, translating into a faster decontamination rate in experiments, over a long period of flow-column operation.

SnxTi1-xO2 solid-solution-nanoparticle embedded mesoporous silica (SBA-15) hybrid as an engineered photocatalyst with enhanced activity.

Synthesis of hybrids of a porous host-material (with well-dispersed embedded nanoparticles inside the pore), wherein each nanoparticle has precisely controlled properties (size and composition) poses a generic challenge. To this end, a new strategy is proposed to form SnxTi1-xO2 solid-solution-nanoparticles inside the pores of sphere-like mesoporous silica (SBA-15), with different percentages of Sn in the nanoparticle (varying from 5 to 50 at%), for enhanced photocatalysis. X-ray diffraction confirms the formation of solid-solution nanoparticles in the porous silica hybrid, while the location of nanoparticles and elemental composition are identified using electron microscopy. The hybrid with 5 at% of Sn (Sn0.05Ti0.95O2-sphere-like SBA-15) shows the maximum photocatalytic activity for degradation of rhodamine-B dye (first order rate constant for degradation, k = 1.86 h(-1)), compared to both pure TiO2-sphere-like SBA-15 (k = 1.38 h(-1)) or pure SnO2-sphere-like SBA-15 (k = 0.14 h(-1)) or other hybrids in this series. XPS and PL spectra suggest the formation of more oxygen vacancies during the replacement of Ti(4+) with Sn(4+). Electrochemical studies reveal that there is a reduction of charge transfer resistance from 910 kΩ cm(-2) for TiO2-sphere-like SBA-15, to 332 kΩ cm(-2) for Sn0.05Ti0.95O2-sphere-like SBA-15. These results imply that the enhancement in photocatalytic performance is as a result of delay in recombination of charge carriers. Therefore, the approach followed in the present work to form solid-solution nanoparticles inside a porous host without causing pore blockage, would be a promising route towards increasing reaction rates in catalytic applications of hybrid materials.

Polyacrylic acid-coated iron oxide nanoparticles for targeting drug resistance in mycobacteria.

The emergence of drug resistance is a major problem faced in current tuberculosis (TB) therapy, representing a global health concern. Mycobacterium is naturally resistant to most drugs due to export of the latter outside bacterial cells by active efflux pumps, resulting in a low intracellular drug concentration. Thus, development of agents that can enhance the effectiveness of drugs used in TB treatment and bypass the efflux mechanism is crucial. In this study, we present a new nanoparticle-based strategy for enhancing the efficacy of existing drugs. To that end, we have developed poly(acrylic acid) (PAA)-coated iron oxide (magnetite) nanoparticles (PAA-MNPs) as efflux inhibitors and used it together with rifampicin (a first line anti-TB drug) on Mycobacterium smegmatis. PAA-MNPs of mean diameter 9 nm interact with bacterial cells via surface attachment and are then internalized by cells. Although PAA-MNP alone does not inhibit cell growth, treatment of cells with a combination of PAA-MNP and rifampicin exhibits a synergistic 4-fold-higher growth inhibition compared to rifampicin alone. This is because the combination of PAA-MNP and rifampicin results in up to a 3-fold-increased accumulation of rifampicin inside the cells. This enhanced intracellular drug concentration has been explained by real-time transport studies on a common efflux pump substrate, ethidium bromide (EtBr). It is seen that PAA-MNP increases the accumulation of EtBr significantly and also minimizes the EtBr efflux in direct proportion to the PAA-MNP concentration. Our results thus illustrate that the addition of PAA-MNP with rifampicin may bypass the innate drug resistance mechanism of M. smegmatis. This generic strategy is also found to be successful for other anti-TB drugs, such as isoniazid and fluoroquinolones (e.g., norfloxacin), only when stabilized, coated nanoparticles (such as PAA-MNP) are used, not PAA or MNP alone. We hence establish coated nanoparticles as a new class of efflux inhibitors for potential therapeutic use.

Improved electrochemical performance of SnO2-mesoporous carbon hybrid as a negative electrode for lithium ion battery applications.

To utilize the high specific capacity of SnO2 as an anode material in lithium-ion batteries, one has to overcome its poor cycling performance and rate capability, which result from large volume expansion (∼300%) of SnO2 during charging-discharging cycles. Hence, to accommodate the volume change during cycling, SnO2 nanoparticles of 6 nm diameter were synthesized specifically only on the outer surface of the mesopores, present within mesoporous carbon (CMK-5) particles, resulting in an effective buffering layer. To that end, the synthesis process first involves the formation of 3.5 nm SnO2 nanoparticles inside the mesopores of mesoporous silica (SBA-15), the latter being used as a template subsequently to obtain SnO2-CMK-5 hybrid particles. SnO2-CMK-5 exhibits superior rate capabilities, e.g. after 30 cycles, a specific discharge capacity of 598 mA h g(-1), at a current density of 178 mA g(-1). Electrochemical impedance spectroscopy reveals that the SnO2-CMK-5 electrode undergoes a significant reduction in solid-electrolyte interfacial and charge transfer resistances, with a simultaneous increase in the diffusion coefficient of lithium ions, all these in comparison to an electrode made of only SnO2 nanoparticles. This enhances the potential of using the SnO2-CMK-5 hybrid as a negative electrode, in terms of improved discharge capacity and cycling stability, compared to other electrodes, such as only SnO2 or only CMK-5.

Gravity-driven packed bed filter, with copper-impregnated activated carbon, for continuous water disinfection in absence of electricity.

Availability of safe drinking water is a major concern in many parts of the world. While many filtration units operating on various principles are available to combat this, most require electricity, which may not be consistently available in such areas. In the present study, we have designed and demonstrated a water disinfection system that can operate purely on gravity, without any electricity. For this, a potassium hydroxide modified copper-impregnated activated carbon (KOH-Cu-AC) hybrid was used as a filter medium for disinfection, because it is less expensive, with performance comparable to previously reported hybrids containing silver. To maintain a constant water flow rate under gravity, during disinfection, a Mariotte bottle was used as the reservoir of the contaminated water. Using this and a constant head between the bottle and the treated water exit point, the required water-filter contact time of 25 min (for decontamination) is maintained in the filter column, regardless of tank-fill level. The demonstrated lab-scale system can perform disinfection of simulated contaminated water (with an initial concentration of 104 CFU mL-1 Escherichia coli), for at least 6 h, with a flow rate of 150 mL h-1. The disinfection performance from the gravity-based filter was further validated with the conventional pump-driven filter, used for continuous disinfection of drinking water. Equivalence of results between pump- and gravity-driven operations helps us to eliminate the need for power, without any compromise in disinfection efficacy. Finally, copper concentration from treated water (106 ppb at steady state) remains very well within the safe limit (1000 ppb as per USEPA guideline). Hence, the lab-scale design of gravity-based packed bed filter will be useful for domestic and community-based supply of safe drinking water in resource-constrained areas, because it eliminated electricity requirement of conventional power-driven systems. PRACTITIONER POINTS: Cost-effective KOH-Cu-AC hybrid is developed as a disinfection material. Mariotte bottle used for maintaining constant disinfected water flow rate works without any electrical power supply. This system can be used for getting on-spot, continuous disinfected water supply. The concentration of copper in the treated water is well within the safety limit. It can be applicable in rural and remote areas (no electric power source) as well as natural calamity-affected areas.

Biosensing of multiple aromatic xenobiotics in water by in-house fabricated prototype device.

Portable, low-cost, and accurate monitoring of hazardous mono-aromatic pollutants, such as phenol or benzene group of compounds in water is a challenging task due to the lack of suitable detectable functional groups and complex matrix of environmental samples. Here, we use a series of protein-based biosensing recognition scaffolds to enable specific detection of several mono-aromatic classes of xenobiotics. The biosensor is tuned to perform in intricate environmental conditions and is interfaced with an in-house manufactured, multi-channel device (AroTrack) capable of direct and sensitive detection of several of these aromatic contaminants, such as phenol, benzene, and 2,3-dimethylphenol (2,3-DMP) in the low ppb range (10-200 ppb). The efficiency of the prototype device was benchmarked in both simulated wastewater and real environmental samples comprising 10 times higher isostructural aromatic pollutants or ions. It was established that AroTrack is reliable for environmental sample testing with a high degree of reproducibility and efficiency comparable to that of modern spectrophotometers (<5 % error). The battery-operated device costs less than $50 to fabricate and this low cost makes it effective to be implemented in rural and low-income settings which suggests immense field deployable potential.

Enhancement of Antimycobacterial Activity of Rifampicin Using Mannose-Anchored Lipid Nanoparticles against Intramacrophage Mycobacteria.

Tuberculosis treatment requires a multidrug combination for the long-term, associated with adverse effects which lead to nonpatient compliance and the emergence of drug-resistant strains. Thus, mannose-anchored rifampicin-loaded solid lipid nanoparticles (M-RIF-SLNs) were developed to enhance the effect of rifampicin by selectively delivering to the macrophage, which led to the high intracellular killing of mycobacteria. The synthesized M-RIF-SLNs show a particle size of ∼100 nm and a drug loading of ∼8%. Cytotoxicity assay confirms that M-RIF-SLNs are not toxic up to 16 µg/mL (equivalent to incorporated rifampicin in SLN) toward THP-1-differentiated macrophages. An antimicrobial assay exhibits a reduction of minimum inhibitory concentration by 4-fold and 8-fold against wild-type and laboratory drug-resistant strains of M. smegmatis, respectively, compared to free rifampicin. Furthermore, mannose-functionalized SLNs loaded with coumarin-6 exhibit a higher macrophage uptake than that of unfunctionalized SLNs. Finally, higher intramacrophage clearance of M. tuberculosis H37Ra was observed with M-RIF-SLNs compared to RIF-SLNs and free rifampicin. Hence, the overall results support that the developed M-RIF-SLNs can be a promising approach for improving the antibacterial activity of rifampicin against intracellular mycobacteria residing in the alveolar macrophages.

pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages.

Nanoparticle deployment in drug delivery is contingent upon controlled drug loading and a desired release profile, with simultaneous biocompatibility and cellular targeting. Iron oxide nanoparticles (IONPs), being biocompatible, are used as drug carriers. However, to prevent aggregation of bare IONPs, they are coated with stabilizing agents. We hypothesize that, zwitterionic drugs like norfloxacin (NOR, a fluoroquinolone) can manifest dual functionality - nanoparticle stabilization and antibiotic activity, eliminating the need of a separate stabilizing agent. Since these drugs have different charges, depending on the surrounding pH, drug loading enhancement could be pH dependent. Hence, upon synthesizing IONPs, they were coated with NOR, either at pH 5 (predominantly as cationic, NOR+) or at pH 10 (predominantly as anionic, NOR-). We observed that, drug loading at pH 5 exceeded that at pH 10 by 4.7-5.7 times. Furthermore, only the former (pH 5 system) exhibited a desirable slower drug release profile, compared to the free drug. NOR-coated IONPs also enable a 22 times higher drug accumulation in macrophages, compared to identical extracellular concentrations of the free drug. Thus, lowering the drug coating pH to 5 imparts multiple benefits - improved IONP stability, enhanced drug coating, higher drug uptake in macrophages at reduced toxicity and slower drug release.

State of dispersion of magnetic nanoparticles in an aqueous medium: experiments and Monte Carlo simulation.

Monte Carlo simulation results predicting the state of dispersion (single, dimer, trimer, and so on) of coated superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles in an aqueous medium are compared with our experimental data for the same. Measured values of the volume percentage of particles in the dispersion, core particle diameter, coating-shell thickness, grafting density of the coating agent, saturation magnetization, and zeta potential for the citric acid-coated and poly(acrylic acid) [PAA]-coated particles have been used in our simulation. The simulation was performed by calculating the total interaction potential between two nanoparticles as a function of their interparticle distance and applying a criterion for the two particles to aggregate, with the criterion being that the minimum depth of the secondary minima in the total interaction potential must be at least equal to k(B)T. Simulation results successfully predicted both experimental trends-aggregates for citric acid-coated particles and an individual isolated state for PAA-coated particles. We have also investigated how this state changes for both kind of coating agents by varying the particle volume percentage from 0.01 to 25%, the particle diameter from 2 to 19 nm, the shell thickness from 1 to 14 nm, and grafting density from 10(15) to 10(22) molecules/m(2). We find that the use of a lower shell thickness and a higher particle volume percentage leads to the formation of larger aggregates. The possible range of values of these four variables, which can be used experimentally to prepare a stable aqueous dispersion of isolated particles, is recommended on the basis of predictions from our simulation.

Development of Mesoporous Silica Nanoparticles of Tunable Pore Diameter for Superior Gemcitabine Drug Delivery in Pancreatic Cancer Cells.

Superior delivery of anticancer drug gemcitabine has been achieved with mesoporous silica nanoparticles (MSN), by addressing three challenges in MSN synthesis: (i) MSN was synthesized with particle diameter between 42 to 64 nm, to utilize enhanced permeability and retention effect of small particles, (ii) MSN of larger internal pore diameter (2.5-5.2 nm) was made as a tunable morphological parameter to optimize both drug loading and its release rate, in a controlled, differential manner and (iii) higher drug release at extracellular cancer-cell pH (5.5) was achieved, compared to physiological pH (7.4) of healthy cells. MSN with above features was made by the sol-gel route, with trimethylmethoxysilane as a size-quencher and hexane or decane as a pore expander. Highest gemcitabine loading of 14.92% and a cumulative release of 58% at pH 5.5 could be obtained with the optimum sample having pore diameter of 5.2 nm, in comparison to the desirably low 22% release at pH 7.4. Consequently, we obtained 60% cell growth-inhibition of pancreatic cancer cell-line (MIA Paca-2), via gemcitabine loaded MSN. This was possible because of increased gemcitabine release from MSN with larger pore diameter of 5.2 nm, simultaneously demonstrating good target-selectivity of MSN as a drug-carrier, due to engineering of its pore-size.

Noninvasive Preclinical Evaluation of Targeted Nanoparticles for the Delivery of Curcumin in Treating Pancreatic Cancer.

Conventional therapy regimens for pancreatic cancer (PC) are surgical resection and systemic gemcitabine based chemotherapy. Recent studies showed that curcumin could potentiate the anticancer effect of gemcitabine in PC. However, due to its poor water solubility, effective bioavailability of curcumin is insufficient, resulting in poor efficacy. To address this issue, mesoporous silica nanoparticles (MSN) were prepared by the sol-gel method, then loaded with curcumin (Cur), coated with polyethylene glycol (PEG), and finally conjugated with the targeting moiety transferrin (Tf) to target human PC cells. TEM analysis revealed that uniform sized spherical MSN formed with an average size of 100 nm, which increased to 120 nm after PEG coating on MSN surface. Confocal microscopy proved that curcumin uptake being seven-times higher for MSN-NH2-Cur-PEG-Tf, when compared to free curcumin. The in vitro cytotoxicity study on MIA PaCa-2 cells showed that MSN-NH2-Cur-PEG-Tf exhibited three-fold higher cytotoxicity than free curcumin. On the basis of the encouraging in vitro cytotoxicity results obtained, preclinical assessment of antitumor efficacy in MIA PaCa-2 subcutaneous xenograft model proves that both MSN-NH2-Cur-PEG and MSN-NH2-Cur-PEG-Tf inhibit tumor growth and minimize distant metastasis to major organ sites. The in vitro studies also proved that nanoparticles can enhance the sensitization effect, caused by curcumin on cancer cells, which help the gemcitabine to kill a higher percentage of cancer cells. Hence, we propose that transferrin targeted, PEGylated, mesoporous silica nanoparticles can be used as a carrier to deliver curcumin, and used in addition to gemcitabine to reduce disease burden significantly for pancreatic cancer patients.

Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy.

Localized cancer rates are on an upsurge, severely affecting mankind across the globe. Timely diagnosis and adopting appropriate treatment strategies could improve the quality of life significantly reducing the mortality and morbidity rates. Recently, nanotherapeutics has precipitously shown increased efficacy for controlling abnormal tissue growth in certain sites in the body, among which ligand functionalized nanoparticles (NP) have caught much attention for improved survival statistics via active targeting. Our focus was to repurpose the antihelminthic drug, niclosamide (NIC), which could aid in inhibiting the abnormal growth of cells restricted to a specific region. The work here presents a one-pot synthesis of niclosamide encapsulated, hyaluronic acid functionalized core-shell nanocarriers [(NIC-PLGA NP)HA] for active targeting of localized cancer. The synthesized nanocarriers were found to possess spherical morphology with mean size of 150.8 ± 9 nm and zeta potential of -24.9 ± 7.21 mV. The encapsulation efficiency was found to be 79.19 ± 0.16% with a loading efficiency of 7.19 ± 0.01%. The nanohybrids exhibited extreme cytocompatibility upon testing with MDA-MB-231 and L929 cell lines. The rate of cancer cell elimination was approximately 85% with targeted cell imaging results being highly convincing. [(NIC-PLGA NP)HA] demonstrates increased cellular uptake leading to a hike in reactive oxygen species (ROS) generation, combating tumour cells aiding in the localized treatment of cancer and associated therapy.

Biofouling prevention using silver nanoparticle impregnated polyethersulfone (PES) membrane: E. coli cell-killing in a continuous cross-flow membrane module.

Biofouling significantly decreases membrane performance. So silver nanoparticle (Ag-NP) was impregnated selectively on a sulfonated polyethersulfone (SPES) membrane and its efficacy was tested in a continuous, cross-flow membrane module. The main challenges are: (i) to prevent biofouling on the membrane surface, (ii) achieve zero bacterial cell (E. coli) count in the permeate water, (iii) maintain Ag concentration in the permeate stream within the permissible limit of drinking water and (iv) maintain a high tensile strength of the membrane to prevent mechanical failure. Addressing these factors would ensure a long and productive service-life of the membrane. To this end, 104CFU/ml of E. coli cell-suspension was passed through the Ag-SPES membrane of 150µm total thickness, which has a narrow (1.74µm thickness), upper surface of Ag-NPs. We achieved zero E. coli cell-count and a minimum (10µg/L) Ag concentration in the permeate stream; simultaneously increasing the tensile strength from 2.78MPa to 3.92MPa due to Ag-NP impregnation. Thus, for a continuous inlet flow of E. coli contaminated water, the membrane module could deliver an almost constant permeate flow rate of 3.45L per hour, due to complete E. coli cell-killing. Simultaneously, Ag concentration in permeate stream is well-below the WHO's recommended limit of 100µg/L, for potable quality water. Therefore, the Ag-SPES membrane can be used as an anti-biofouling membrane in a continuous operational mode.