Vikas Beniwal

Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer.

Curcumin, a derived product from common spice turmeric that is safe and beneficial in several aliments was formulated into biodegradable nanoparticles with a view to improve its oral bioavailability. The curcumin encapsulated nanoparticles prepared by emulsion technique were spherical in shape with particle size of 264nm (polydispersity index 0.31) and 76.9% entrapment at 15% loading. The curcumin encapsulated nanoparticles were able to withstand the International Conference on Harmonisation (ICH) accelerated stability test conditions for refrigerated products for the studied duration of 3 months. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The in vitro release was predominantly by diffusion phenomenon and followed Higuchis release pattern. The in vivo pharmacokinetics revealed that curcumin entrapped nanoparticles demonstrate at least 9-fold increase in oral bioavailability when compared to curcumin administered with piperine as absorption enhancer. Together the results clearly indicate the promise of nanoparticles for oral delivery of poorly bioavailable molecules like curcumin.

Design of biodegradable nanoparticles for oral delivery of Doxorubicin: in vivo pharmacokinetics and toxicity studies in rats

PurposeDoxorubicin, a potent anticancer drug associated with cardiotoxicity and low oral bioavailability, was loaded into nanoparticles with a view to improve its performance.MethodsDoxorubicin loaded PLGA nanoparticles were prepared by a double emulsion method. The pH dependent stability of nanoparticles in simulated fluids was evaluated. DSC and XRD studies were carried out in order to ascertain the nature of doxorubicin in formulations in conjunction with accelerated stability studies. The in vitro release was investigated in phosphate buffer. The pharmacokinetic and toxicity studies were conducted in rats.ResultsNanoparticles had an average size of 185xa0nm, with 49% entrapment at 10% w/w of polymer. The particles displayed good pH dependent stability in the pH range 1.1–7.4. DSC and XRD studies revealed the amorphous nature of doxorubicin in nanoparticles and the accelerated stability studies revealed the integrity of formulations. Initial biphasic release (20%) followed by a sustained release (80%) for 24xa0days was observed under in vitro conditions. The doxorubicin loaded nanoparticles demonstrated superior performance in vivo as evident by enhanced bioavailability and lower toxicity.ConclusionsTogether, the data indicates the potential of doxorubicin loaded nanoparticles for oral chemotherapy. Further, these formulations could be explored for new indications like leishmaniasis.

Microbial pigments as natural color sources: current trends and future perspectives

Synthetic colors have been widely used in various industries including food, textile, cosmetic and pharmaceuticals. However toxicity problems caused by synthetic pigments have triggered intense research in natural colors and dyes. Among the natural Sources, pigment producing microorganisms hold a promising potential to meet present day challenges. Furthermore natural colors not only improve the marketability of the product but also add extra features like anti oxidant, anti cancer properties etc. In this review, we present various sources of microbial pigments and to explore their biological and clinical properties like antimicrobial, antioxidant, anticancer and anti inflammatory. The study also emphasizes upon key parameters to improve the bioactivity and production of microbial pigments for their commercial use in pharmacological and medical fields.

Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: antibacterial, DNA photocleavage, and anticancer activities.

In continuation of our efforts to find new biologically active agents, regioselective synthesis of a series of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones 4a-k has been achieved under facile, extremely mild and greener reaction conditions with excellent yields. Moreover, one pot multicomponent reaction has also been reinvestigated under previously reported solvent conditions to prepare 4a-b and found that the reaction generates significant amount of side products. The chemical structures of 4a-k were established on the basis of a combined use of IR, NMR ((1)H, (13)C) spectroscopy, mass spectrometry and elemental analysis. All the compounds were evaluated for their antibacterial, DNA photocleavage and anticancer activities. Among all, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-(naphth-2-yl)ethanone 4j displayed good inhibitory profile against Escherichia coli and Staphylococcus aureus which was about 50% and 25% of the Ampicillin (standard drug), respectively. The compounds, 4a and 4f showed relatively moderate inhibition against Psuedomonas aeruginosa and E.xa0coli. In DNA photocleavage study, compounds 4c and 4d were found to be highly active and completely degraded both forms of DNA (SC and OC), even at a very low concentration of 1xa0μg (4c) under irradiation of UV light. However, 4h and 4f resulted in complete DNA degradation at 30xa0μg concentration. Moreover, 4h showed fluorescence at 15xa0μg concentration and increased the intensity of both bands of DNA (SC and OC) as compared to control. On the other hand, to valorize the biological potential, the compounds were screened for their cytotoxic activity on colon (HCT116 and HT29), prostate (DU145), ovarian (SKOV3) and lung (A549) cancer cell lines. The compound 4j was found to be cytotoxic to all the cancer cell lines, except SKOV3, with more selectivity towards the colon cancer cell lines (HCT116, HT29) and A549 lung cancer cell line. On A549 lung cancer cell line, 4j and 4k exhibited similar potency as carboplatin in inhibiting cell viability.

PRODUCTION OF TANNASE UNDER SOLID-STATE FERMENTATION AND ITS APPLICATION IN DETANNIFICATION OF GUAVA JUICE

Guava juice is known to be rich in antioxidant activity due a high level of vitamins A and C. However, tannins present in the guava juice form tannin–protein complexes that affect the utilization of vitamins and minerals and inhibit digestive enzymes. Beside this, bitterness and cloudiness are the other major problems of juice industries. The present study aimed to utilize a low-cost substrate (tea residue) for the production of tannase and its application in detannification of guava juice. Solid-state fermentation (SSF) was evaluated to produce tannase from Aspergillus niger. Maximum tannase (1.86 U/g dry substrate) production was observed at 30°C after 96 hr of the incubation period. The optimum pH of the moistening agent was found to be 5.0. Partially purified enzyme using ammonium sulfate precipitation was subjected to guava juice treatment at a level of 0.5, 1.0, and 2.0% for 30 and 60 min. Decrease in tannic acid content of guava juice was found to be 17.60, 29.04, and 44.38% after 30 min and 40.59, 53.69, and 59.23% after 60 min, respectively.

Optimization of tannase production by a novel Klebsiella pneumoniae KP715242 using central composite design

A novel tannase producing bacterial strain was isolated from rhizospheric soil of Acacia species and identified as Klebsiella pneumoniae KP715242. A 3.25-fold increase in tannase production was achieved upon optimization with central composite design using response surface methodology. Four variables namely pH, temperature, incubation period, and agitation speed were used to optimize significant correlation between the effects of these variables on tannase production. A second-order polynomial was fitted to data and validated by ANOVA. The results showed a complex relationship between variables and response given that all factors were significant and could explain 99.6% of the total variation. The maximum production was obtained at 5.2 pH, 34.97 °C temperature, 103.34 rpm agitation speed and 91.34 h of incubation time. The experimental values were in good agreement with the predicted ones and the models were highly significant with a correlation coefficient (R2) of 0.99 and a highly significant F-value of 319.37.

Synthesis, characterization and DNA photocleavage study of a novel dehydroacetic acid based hydrazone Schiff’s base and its metal complexes

A series of some novel colored complexes of Co(II), Ni(II), Cu(II), Mn(II) and Zn(II) with a novel dehydroacetic acid based hydrazone Schiff’s base has been synthesized and evaluated for their DNA photocleavage potential. The ligand utilized in the present investigation was synthesized via a condensation reaction between cyanoacetic acid hydrazide and dehydroacetic acid. Further, the ligand was treated with different metal acetates of first transition series in 1:1 and 1:2 (metal to ligand) ratios, respectively, to obtain metal complexes with different ligand to metal stoichiometry. Ligand as well as all the synthesized metal complexes were characterized on the basis of data obtained from the techniques like 1H and 13C NMR, IR spectroscopy, mass spectrometry, UV visible spectroscopy, elemental analysis and molar conductance. 1H NMR spectrum of Zn(II) complexes showed the coordination of enolic oxygen atom without deprotonation, but in case of DLCu, the deprotonation of enolic proton was occurred prior to coordination. IR data revealed the participation of a carbonyl oxygen atom of ligand in coordination with metal ions. UV visible data confirmed the square-planar and octahedral geometry of the complexes. Mass spectrum showed the formation of both 1:1 and 1:2 metals to ligand stoichiometry. Most of metal complexes exhibited very good DNA photocleavage activities.

Production of tannase through solid state fermentation using Indian Rosewood ( Dalbergia Sissoo )sawdust—a timber industry waste

The tannase producing strain Aspergillus heteromorphus MTCC 8818 was used in the present study for the production of tannase under solid state fermentation using Rosewood (Dalbergia sissoo) sawdust—a timber industry waste—as substrate. Various physico-chemical parameters were optimized for extracellular yield of tannase. Maximum tannase (1.84 U/g dry substrate) and gallic acid (5.4xa0mg/g ds) was observed at 30xa0°C after 96xa0h of incubation. Czapek dox medium was found to be the best moistening agent, with pH and relative humidity of 5.5 and 70xa0%, respectively. The constituents of Czapek dox medium were varied to enhance enzyme production. The optimum concentration of modified Czapek dox constituents contained 0.2xa0% NaNO3, 0.05xa0% K2HPO4 and MgSO4, 0.15xa0% KCl. Among the additional salts supplemented to Czapek dox medium, ZnSO4 and CuSO4 were found to have a stimulating effect, with a relative tannase activity of 116 and 111xa0%, respectively. Glucose as an external carbon source was found to be a repressor of enzyme production.

Identification of novel single nucleotide polymorphisms in the DGAT1 gene of buffaloes by PCR-SSCP

Diacylglycerol O-acyltransferase 1 (DGAT1) is a microsomal enzyme that catalyzes the final step of triglyceride synthesis. The DGAT1 gene is a strong functional candidate for determining milk fat content in cattle. In this work, we used PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) and DNA sequencing to examine polymorphism in the region spanning exon 7 to exon 9 of the DGAT1 gene in Murrah and Pandharpuri buffaloes. Three alleles (A, B and C) and four novel single-nucleotide polymorphisms were identified in the buffalo DGAT1 gene. The frequencies of the alleles differed between the two buffalo breeds, with allele C being present in Murrah but not in Pandharpuri buffalo. The allele variation detected in this work may influence DGAT1 expression and function. The results described here could be useful in examining the association between the DGAT1 gene and milk traits in buffalo.

Synthesis, docking study, and DNA photocleavage activity of some pyrimidinyl hydrazones and 3-(quinolin-3-yl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine derivatives

In the present study, synthesis of a series of some novel 3-(Quinolin-3-yl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine derivatives (4a–e) has been achieved by oxidative cyclization of new pyrimidinyl hydrazone intermediates (3a–e) using hypervalent iodine reagent(III) under mild conditions. The structures of all synthesized compounds were established on the basis of IR, NMR (1H and 13C), mass spectral data, and elemental analysis. All compounds were evaluated for their DNA photocleavage activity. Compounds 4a, 4b, 4d and 3a–e were found to possess good activity at 40xa0μg/μl concentration and were mainly responsible for the conversion of supercoiled form of DNA into open circular form. Further, docking study was carried out using Molegro Virtual Docker version 2010.4.2.0 using PDB (1AB4) in support of the results obtained.