Asoke P. Chattopadhyay

Surface tunability of nanoparticles in modulating platelet functions

Metallic nanoparticles are attractive candidates as MRI contrast agents and mediators for drug delivery, diagnostics, and therapy. Direct contact and exposure to blood circulation is common in many such applications. The consequent thrombotic response may therefore be important to study. The main objective of the present work was to study how platelet functions were changed in the presence of different nano-surface or surface capping, which may provide a measure for the safety of a nanoparticle, and also assess the use of such nanoparticles in platelet modulation. Aggregometry, ATP release reaction, flow cytometry and immune-blotting studies were performed to study platelet response to different nano-particles (iron oxide, gold and silver). For each nanoparticle surface conjugation (capping) was varied. It was found that citric acid functionalized iron oxide nanoparticles have anti-platelet activity, with a decrease in aggregation, tyrosine phosphorylation level, and granule release. On the other hand in other cases (e.g. gold nanoparticles) pro-aggregatory response was observed in the presence of nanoparticles and, in some cases, the nanoparticles behaved neutrally (e.g. for starch-coated iron oxide nanoparticles). Therefore, nanoparticles can induce antiplatelet or a pro-aggregatory response, or remain neutral depending on surface capping. A related observation is that antiplatelet drugs can be made more potent by nanoparticle conjugation.

Therapeutic efficacy of artemisinin-loaded nanoparticles in experimental visceral leishmaniasis

Visceral leishmaniasis (VL) is a fatal vector-borne parasitic syndrome attributable to the protozoa of the Leishmania donovani complex. The available chemotherapeutic options are not ideal due to their potential toxicity, high cost and prolonged treatment schedule. In the present study, we conjectured the use of nano drug delivery systems for plant-derived secondary metabolite; artemisinin as an alternative strategy for the treatment of experimental VL. Artemisinin-loaded poly lactic co-glycolic acid (ALPLGA) nanoparticles prepared were spherical in shape with a particle size of 220.0±15.0 nm, 29.2±2.0% drug loading and 69.0±3.3% encapsulation efficiency. ALPLGA nanoparticles administered at doses of 10 and 20mg/kg body weight showed superior antileishmanial efficacy compared with free artemisinin in BALB/c model of VL. There was a significant reduction in hepatosplenomegaly as well as in parasite load in the liver (85.0±5.4%) and spleen (82.0±2.4%) with ALPLGA nanoparticles treatment at 20mg/kg body weight compared to free artemisinin (70.3±0.6% in liver and 62.7±3.7% in spleen). In addition, ALPLGA nanoparticle treatment restored the defective host immune response in mice with established VL infection. The protection was associated with a Th1-biased immune response as evident from a positive delayed-type hypersensitivity reaction, escalated IgG2a levels, augmented lymphoproliferation and enhancement in proinflammatory cytokines (IFN-γ and IL-2) with significant suppression of Th2 cytokines (IL-10 and IL-4) after in vitro recall, compared to infected control and free artemisinin treatment. In conclusion, our results advocate superior efficacy of ALPLGA nanoparticles over free artemisinin, which was coupled with restoration of suppressed cell-mediated immunity in animal models of VL.

A new approach for the delivery of artemisinin: Formulation, characterization, and ex-vivo antileishmanial studies

HYPOTHESIS Artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. Encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity. EXPERIMENTS Artemisinin-loaded nanoparticles were prepared, optimized (using Box-Behnken design) and characterized by dynamic light scattering technique, Atomic force microscopy (AFM), Transmission electron microscopy (TEM) and Fourier Transform-Infra Red spectroscopy. Release kinetics of artemisinin from optimized nanoformulation was studied by dialysis method at pH 7.4 and 5.5. Cytotoxicity and antileishmanial activity of these nanoparticles was tested on murine macrophages by MTT assay and macrophage-infested Leishmania donovani amastigotes ex vivo, respectively. FINDINGS Artemisinin-loaded nanoparticles were 221±14nm in diameter, with polydispersity index, zeta potential, drug loading and entrapment efficiency of 0.1±0.015, -9.07±0.69mV, 28.03±1.14 and 68.48±1.97, respectively. AFM and TEM studies indicated that the particles were spherical in shape. These colloidal particles showed a sustained release pattern in vitro. Treatment with artemisinin-loaded nanoparticles significantly reduced the number of amastigotes per macrophage and percent infected macrophages ex vivo compared to free artemisinin. These nanoparticles were also non-toxic to macrophages compared to artemisinin alone.

Quinoline based receptor in fluorometric discrimination of carboxylic acids

Summary Quinoline and naphthalene-based fluororeceptors 1 and 2 have been designed and synthesized for detection of hydroxy carboxylic acids in less polar solvents. The receptor 1 shows monomer emission quenching followed by excimer emission upon hydrogen bond-mediated complexation of carboxylic acids. The excimer emission distinguishes aromatic dicarboxylic acids from aliphatic dicarboxylic acids and even long chain aliphatic dicarboxylic acids from short chain aliphatic dicarboxylic acids. The receptor 1 is found to be selective for citric acid with a strong excimer emission in CHCl3. On the contrary, the receptor 2 exhibited less binding constant value and did not form any excimer upon complexation with the same acids under similar conditions. This established the role of quinoline ring nitrogen in binding with the acids.

Coumarin based emissive rod shaped new schiff base mesogens and their zinc(II) complexes: synthesis, photophysical, mesomorphism, gelation and DFT studies

ABSTRACT New homologous series of coumarin Schiff base derived from 6-aminocoumarin and their zinc(II) complexes have been synthesised. The spectroscopic characterisations, photophysical properties, phase transition temperature, characterisation of phase and gelation behaviour are reported. The ligand is non-mesogenic at lower 4-n-alkoxy chain length (n = 4) and mesogenic for longer chains (n > 4). For small chains (n = 5, 7, 8), ligand displays monotropic nematic or nematic-smectic A phase sequences, whereas longer homologues (n = 12, 14, 16 and 18) display only enantiotropic smectic A phase. The ligands and their Zn(II) complexes are fluorescent in nature. Interestingly, ligands exhibit gelation property only in polar solvents, whereas Zn(II) complexes discourage gelation. The effect of 4-n-alkoxy chain length on the gelation properties was also discussed. Density functional theory calculations show broad agreement with observed molecular conformation, dipole moment, molecular orbitals and polarisability of the coumarin Schiff base molecules and their Zn(II) complexes. GRAPHICAL ABSTRACT

Anthracene appended pyridinium amide-urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt.

Summary A new anthracene labeled pyridinium amide–urea conjugate 1 has been designed and synthesized. The receptor shows a different fluorometric response with L-N-acetylvaline and L-N-acetylalanine salts in CH3CN in contrast to the other salts of L-N-acetyl α-amino acids and (S)-α-hydroxy acids studied. Upon complexation of the tetrabutylammonium salt of L-N-acetylvaline, the emission of 1 increases accompanied by the formation of a new band at higher wavelength and this characteristic change distinguishes it from other anionic substrates studied. The binding interaction has been studied by 1H NMR, fluorescence and UV titration experiments.

Depletion of Soil Potassium under Exhaustive Cropping in Inceptisol and Alfisol

Pot-culture studies of intensive cropping without potassium (K) application, taking three successive crops of rice on Sonakhali (Inceptisol) and Ranibundh (Alfisol) soils, revealed that all the forms of soil K declined after the third crop compared to the corresponding initial soil status. A similar trend was also found for nonexchangeable K extracted sequentially and termed as Step K and CR-K (constant rate K). The CR-K contents showed little variations with cropping. Except for the potential buffering capacity of the soil for K at equilibrium (PBCK 0) values, all the quantity/intensity (Q/I) parameters, namely activity ratio of potassium (ARK e), labile K (–ΔK0), specifically held K (KX), and total labile pool of K (KL) values, decreased in both the soils as they were subjected to repeated cropping. The PBCK 0 values changed to a smaller extent in both the soils. In both soils, the threshold levels for release of intermediate K in terms of activity ratio, exchangeable K, and K concentration in soil solution decreased after the third cropping as compared to the initial status. The dry-matter weight of rice, K concentration, and K uptake decreased with the cropping sequence. The difference in values of each parameter between initial status and the third crop was much wider in Inceptisol than in Alfisol.

Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of −27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.

Target synthesis of biocompatible spherical bismuth sulphide nanoparticles for biological application

Bismuth sulphide nanoparticles are prepared by sol–gel method using gelatine as capping agent. Synthesized nanoparticles are well dispersed in water and the medium is nearly neutral, both essential for biological application. Triethanolamine is used as a complexing agent for solubilization of Bi3+ in water and sodium sulphide as a sulphur source. Nanoparticles are well characterized by standard methods and show marked cytotoxicity and alter membrane potentials of both mitochondria and HeLa cells.Graphical AbstractSchematic route to synthesize water-soluble Bi2S3 nanoparticles

Liming Effects on Extractable Boron in Six Acidic Soils

A laboratory incubation study was conducted to study the influence of liming on extractable boron (B) in acidic soil. Six soils, three each from the Inceptisols and Alfisols, were incubated for 30 days with combinations of lime and B. The soils were acutely deficient in plant-available B (0.09–0.21 mg kg−1). Only <50 percent of applied B was recovered from the soils in available form. Such recovery was lower in Alfisols than that in Inceptisols due to adsorption of a greater amount of added B with iron (Fe−) and aluminium (Al−) oxides in the former soil group. Required dose of lime showed an increase in availability of native soil B, particularly in Inceptisols (26 percent), and a net decrease in recovery of added B (32.5 percent) as compared to no lime control (41.6 percent). The results thus suggest that liming to acidic soils increases extractable B.