Parduman Raj Sharma

Highly Selective Fluorescence Turn-on Chemodosimeter Based on Rhodamine for Nanomolar Detection of Copper Ions

A highly selective fluorescent chemodosimeter based on rhodamine is synthesized which undergoes Cu(2+) driven hydrolysis in aqueous media to produce fluorescence turn-on changes with a detection limit up to the nanomolar range.

Dual Targeted Polymeric Nanoparticles Based on Tumor Endothelium and Tumor Cells for Enhanced Antitumor Drug Delivery

Some specific types of tumor cells and tumor endothelial cells represented CD13 proteins and act as receptors for Asn-Gly-Arg (NGR) motifs containing peptide. These CD13 receptors can be specifically recognized and bind through the specific sequence of cyclic NGR (cNGR) peptide and presented more affinity and specificity toward them. The cNGR peptide was conjugated to the poly(ethylene glycol) (PEG) terminal end in the poly(lactic-co-glycolic) acid PLGA-PEG block copolymer. Then, the ligand conjugated nanoparticles (cNGR-DNB-NPs) encapsulating docetaxel (DTX) were synthesized from preformed block copolymer by the emulsion/solvent evaporation method and characterized for different parameters. The various studies such as in vitro cytotoxicity, cell apoptosis, and cell cycle analysis presented the enhanced therapeutic potential of cNGR-DNB-NPs. The higher cellular uptake was also found in cNGR peptide anchored NPs into HUVEC and HT-1080 cells. However, free cNGR could inhibit receptor mediated intracellular uptake of NPs into both types of cells at 37 and 4 °C temperatures, revealing the involvement of receptor-mediated endocytosis. The in vivo biodistribution and antitumor efficacy studies indicated that targeted NPs have a higher therapeutic efficacy through targeting the tumor-specific site. Therefore, the study exhibited that cNGR-functionalized PEG-PLGA-NPs could be a promising approach for therapeutic applications to efficient antitumor drug delivery.

Anticancer activity of an essential oil from Cymbopogon flexuosus.

The essential oil from a lemon grass variety of Cymbopogon flexuosus was studied for its in vitro cytotoxicity against twelve human cancer cell lines. The in vivo anticancer activity of the oil was also studied using both solid and ascitic Ehrlich and Sarcoma-180 tumor models in mice. In addition, the morphological changes in tumor cells were studied to ascertain the mechanism of cell death. The in vitro cytotoxicity studies showed dose-dependent effects against various human cancer cell lines. The IC(50) values of oil ranged from 4.2 to 79 microg/ml depending upon the cell line. In 502713 (colon) and IMR-32 (neuroblastoma) cell lines, the oil showed highest cytotoxicity with IC(50) value of 4.2 and 4.7 microg/ml, respectively. Intra-peritoneal administration of the oil significantly inhibited both ascitic and solid forms of Ehrlich and Sarcoma-180 tumors in a dose-dependent manner. The tumor growth inhibition at 200 mg/kg (i.p.) of the oil observed with both ascitic and solid tumor forms of Ehrlich Ascites carcinoma was 97.34 and 57.83 respectively. In case of Sarcoma-180, the growth inhibition at similar dose of oil was 94.07 and 36.97% in ascitic and solid forms respectively. Morphological studies of the oil treated HL-60 cells revealed loss of surface projections, chromatin condensation and apoptosis. The mitochondria showed apparent loss of cristae in the cells undergoing apoptosis. The morphological studies of Sarcoma-180 solid tumor cells from animals treated with the oil revealed condensation and fragmentation of nuclei typical of apoptosis. Morphological studies of ascites cells from animals treated with the oil too revealed the changes typical of apoptosis. Our results indicate that the oil has a promising anticancer activity and causes loss in tumor cell viability by activating the apoptotic process as identified by electron microscopy.

New Fluorogenic Sensors for Hg2+ Ions: Through-Bond Energy Transfer from Pentaquinone to Rhodamine

New pentaquinone derivatives 5 and 8 having rhodamine moieties have been designed and synthesized that undergo through-bond energy transfer (TBET) in the presence of Hg(2+) ions among the various cations (Cu(2+), Pb(2+), Fe(2+), Fe(3+), Zn(2+), Ni(2+), Cd(2+), Co(2+), Ag(+), Ba(2+), Mg(2+), K(+), Na(+), and Li(+)) tested in mixed aqueous media.

Recognition of adenosine monophosphate and H2PO4- using zinc ensemble of new hexaphenylbenzene derivative: potential bioprobe and multichannel keypad system.

Zinc ensemble of hexaphenylbenzene derivative 3 exhibits sensitive response toward adenosine monophosphate (AMP) and H(2)PO(4)(-) ions. Further, the application of derivative 3 as a multichannel molecular keypad could be realized in the presence of inputs of Zn(2+) ions, H(2)PO(4)(-) ions, and AMP.

Enhanced anticancer potential of encapsulated solid lipid nanoparticles of TPD: a novel triterpenediol from Boswellia serrata.

A pentacyclic triterpenediol (TPD) from Boswellia serrata has significant cytotoxic and apoptotic potential in a large number of human cancer cell lines. To enhance its anticancer potential, it was successfully formulated into solid lipid nanoparticles (SLNs) by the microemulsion method with 75% drug entrapment efficiency. SEM and TEM studies indicated that TPD-SLNs were regular, solid, and spherical particles in the range of 100-200 nm, and the system indicated that they were more or less stable upon storing up to six months. TPD loaded SLNs showed significantly higher cytotoxic/antitumor potential than the parent drug. TPD-SLNs have 40-60% higher cytotoxic and apoptotic potential than the parent drug in terms of IC(50), extent of apoptosis, DNA damage, and expression of pro-apoptotic proteins like TNF-R1, cytochrome-c, and PARP cleavage in HL-60 cells. Moreover, blank SLNs did not have any cytotoxic effect on the cancer as well as in normal mouse peritoneal macrophages. The in vivo antitumor potential of TPD-SLNs was significantly higher than that of TPD alone in Sarcoma-180 solid tumor bearing mice. Therefore, SLNs of TPD successfully increased the apoptotic and anticancer potential of TPD at comparable doses (both in vitro and in vivo). This work provides new insight into improvising the therapeutic efficacy of TPD by adopting novel delivery strategies such as solid lipid nanoparticles.

Cytotoxic and apoptotic activity of essential oil from Ocimum viride towards COLO 205 cells

We investigated the apoptosis inducing effect of essential oil (EO) from aerial parts of Ocimumviride in human colorectal adenocarcinoma cells (COLO 205 cell line). The COLO 205 cells were exposed to 0.0125-0.1 microl/ml of EO for 24, 48 and 72h. Growth inhibition was determined by sulphorhodamine B (SRB) assay. Double staining with acridine orange and ethidium bromide for nuclear changes was performed. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, the proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. Eventually the surface morphology of apoptotic cells was studied by scanning electron microscopy. EO is cytotoxic to COLO 205 cells in dose and time-dependent manner, as is evident by SRB assay. This observed cell death was due to apoptosis, as established by annexin V/PI assay, DNA ladder formation and scanning electron microscopy. Our results reveal that EO has apoptosis inducing effect against COLO 205 cells in vitro and is a promising candidate for further anti-cancer study.

Development and evaluation of folate functionalized albumin nanoparticles for targeted delivery of gemcitabine

Gemcitabine is one of the most potent anticancer agents acting on a wide range of solid tumors, however, its use is limited by short half life and high dose leading to serious side effects. The present investigation describes the development and characterization of folate functionalized gemcitabine loaded bovine serum albumin nanoparticles (Fa-Gem-BSANPs). The nanoparticles were prepared by desolvation cross-linking technique and characterized for various parameters including morphology, particle size, zeta potential, drug loading and release profile. The particle size of Gem-BSANPs and Fa-Gem-BSANPs was found to be 159.1±5.29 and 208.7±1.80 nm, respectively. DSC and XRD analysis indicated amorphous nature of the drug within the particles. The encapsulated gemcitabine exhibited less hemolytic properties as compared to native drug. The anticancer activity of Fa-Gem-BSANPs was evaluated in folate receptor over expressing cell lines (Ovcar-5 and MCF-7) and folate receptor deficient cell line (MIAPaCa-2). The Fa-Gem-BSANPs showed superior anticancer activity as compared to Gem-BSANPs in Ovcar-5 and MCF-7 cells while no significant difference in cytotoxicity was found with MIAPaCa-2 cells. Confocal microscopy indicated facilitated intracellular uptake of Fa-Gem-BSANPs in MCF-7, which in turn result in a higher potential for apoptosis. Further, Fa-Gem-BSANPs exhibited improved anti-tumor activity in Ehrlich solid tumor model in mice. In conclusion, our study indicates that folate functionalized nanoparticles confer enhance cellular uptake and cytotoxicity for gemcitabine.

A universal solid support for the synthesis of 3'-thiol group containing oligonucleotides

Abstract Use of a derivatised polymer support 5 involving the 4,4′-dimethoxytrityloxypentyl-3-mercaptopropionamide group allows the automated synthesis of oligonucleotides bearing thiol group at their 3′-termini.

Temperature induced sterilization for control of three stored grain beetles

Abstract Pupae (1, 2 and 3 days old) of three stored grain beetles, Trogoderma granarium, Tribolium castaneum and Callosobruchus chinensis, were subjected to temperatures of 30, 40 and 45°C with an exposure period of 24, 48 and 72 h for each age-group. Observations of adult emergence and their progeny revealed that though all the temperatures were effective in causing sterility, exposure to 45°C was particularly effective in suppressing adult formation. With T. castaneum and C. chinensis, adult emergence was totally prevented by 48 and 72 h exposures to 45°C. With T. granarium, the inhibitory effect was greater with male pupae and the resultant adults were completely sterile.