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71.
Priyanka Pandya Surendra Gattani Pankaj Jain Lokesh Khirwal Sanjay Surana 《AAPS PharmSciTech》2008,9(4):1247-1252
A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility,
dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility
and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer
hydroxypropyl methylcellulose (HPMC K3LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of
HPMC K3LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state
was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy,
and Fourier-transform infrared spectroscopy. In vitro–in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of
the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased
in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol
and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug
and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces
amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM. 相似文献
72.
Cloning of a cuticle-degrading protease from the entomopathogenic fungus, Beauveria bassiana 总被引:7,自引:0,他引:7
Lokesh Joshi Raymond J. St. Leger Michael J. Bidochka 《FEMS microbiology letters》1995,125(2-3):211-217
Abstract A Beauveria bassiana extracellular subtilisin-like serine endoprotease is a potential virulence factor by virtue of its activity against insect cuticles. A cDNA clone of the protease was isolated from mycelia of B. bassiana grown on cuticle/chitin cultures. The amino acid sequence of this gene was compared to that of Metarhizium anisopliae Pr1, the only pathogenicity determinant so far described from an entomopathogenic fungus, and proteinase K, isolated from Tritirachium album , a saprophytic fungus. The cDNA sequence revealed that B. bassiana Prl is synthesized as a large precursor ( M r 37 460) containing a signal peptide, a propeptide and the mature protein predicted to have an M r of 26 832. 相似文献
73.
Rajesh Lokesh K. Gangwar Sujeet K. Mishra Amit Choudhary Ashok M. Biradar Gajjala Sumana 《Luminescence》2023,38(7):811-833
The application of liquid crystal (LC) materials has undergone a modern-day renaissance from its classical use in electronics industry as display devices to new-fangled techniques for optically detecting biological and chemical analytes. This review article deals with the emergence of LC materials as invaluable material for their use as label-free sensing elements in the development of optical, electro-optical and electrochemical biosensors. The property of LC molecules to change their orientation on perturbation by any external stimuli or on interaction with bioanalytes or chemical species has been utilized by many researches for the fabrication of high sensitive LC-biosensors. In this review article we categorized LC-biosensor based on biomolecular reaction mechanism viz. enzymatic, nucleotides and immunoreaction in conjunction with operating principle at different LC interface namely LC-solid, LC-aqueous and LC-droplets. Based on bimolecular reaction mechanism, the application of LC has been delineated with recent progress made in designing of LC-interface for the detection of bio and chemical analytes of proteins, virus, bacteria, clinically relevant compounds, heavy metal ions and environmental pollutants. The review briefly describes the experimental set-ups, sensitivity, specificity, limit of detection and linear range of various viable and conspicuous LC-based biosensor platforms with associated advantages and disadvantages therein. 相似文献
74.
75.
Joe Bina Rao Ummiti J.S.P. Lokesh Belur R. 《Molecular and cellular biochemistry》1997,166(1-2):125-134
Voltage-dependent L-type Ca2+ channels form highly selective pores for Ca2+ ions in the membranes of excitable cells. We investigated the functional role of negatively charged residues, within or near the selectivity region, in ion permeation of a human cardiac L-type Ca2+ channel. Glutamates in each of the four repeats, and an aspartate in repeat IV, were substituted with positively charged lysine. Wild-type and mutant Ca2+ channels were expressed in Xenopus oocytes. Block by Ca2+ and Mg2 of inward Li+ currents through the channels was used to assess the effects of amino acid substitutions on high-affinity divalent cation binding. The rank order of IC50's for Ca2+ block of ILi was: E677K > E1086K > E334K > E1387K > D1391K > wild-type. The order of IC50's for Mg2+ block of ILi indicated differential involvement of the same residues in Mg2+ binding: E1387K > E334K > E1086K > E677K > D1391K wild-type. Mutants E1387K and D1391K effectively permeated Ba2+, but exhibited a decreased single-channel conductance. The unitary current amplitude carried by Na+, in the absence of external divalent cations, was slightly decreased in the E1387K mutant but not in the D1391K mutant. The results confirm that each of the four glutamates participate unequally in high-affinity Ca2+ binding. Additionally, our results indicate that these glutamate residues participate in Mg2+ binding. The glutamate at position 1387 may be only peripherally involved in the formation of a high-affinity Ca2+ -binding site but is central to a Mg2+ binding site accessible from the external side of the pore. The aspartate at position 1391 is most likely located just external to the selectivity region. (Mol Cell Biochem 166: 125-134, 1997) 相似文献
76.
Exogenous arachidonic acid induced the synthesis of a 120 000 molecular weight protein in resident peritoneal macrophages. The induction of this protein is specific to the presence of arachidonic acid in the culture medium and is not induced by the presence of other fatty acids, irrespective of their chain length or degree of unsaturation. The protein induced is not a secretory protein and is not formed as a result of the processing of preexisting proteins in macrophages. In addition to arachidonic acid, prostaglandin E2 also induced the synthesis of 120 000 molecular weight protein in macrophages. 相似文献
77.
Raymond J.St. Leger Susumu Shimizu Lokesh Joshi Michael J. Bidochka Donald W. Roberts 《FEMS microbiology letters》1995,131(3):289-294
Abstract The potential of β-glucuronidase as a molecular marker for studying the environmental microbiology of entomopathogenic fungi was assessed. Metarhizium anisopliae was stably co-transformed with plasmids (pNOM102 and pBENA3) containing the β-glucuronidase and benomyl resistance (β-tubulin) genes, using both electroporation and biolistic delivery systems, and it was confirmed that the expressed phenotypes were not exhibited by ten randomly chosen indigenous North-American isolates. In spite of random and multiple integrations, the co-transformants showed normal growth rates and retained their pathogenicity to insects. β-Glucuronidase activity in the co-transformants was used to detect histochemically the presence of fungal hyphae in infected host insects ( Bombyx mori ) and thus provides a practical means of marking genetically engineered pathogens for field trials. 相似文献
78.
79.
Kilcoyne M Shah M Gerlach JQ Bhavanandan V Nagaraj V Smith AD Fujiyama K Sommer U Costello CE Olszewski N Joshi L 《Journal of plant physiology》2009,166(3):219-232
Mucin-type O-glycosylation has been well characterized in mammalian systems but not in plants. In this study, the purified alcohol-soluble, non-reduced protein (prolamin) fraction from rice seed was investigated for the occurrence of O-linked oligosaccharides. As storage prolamins are unlikely to be O-glycosylated, any O-glycosylation found was likely to belong to co-extracted proteins, whether because of association with the protein body or solubility. SDS-PAGE and MS analyses revealed 14 and 16kDa protein families in fractions that bound to the lectins peanut agglutinin (PNA), Vicia villosa lectin (VVL) and Jacalin, indicative of the presence of O-linked saccharides. Enzymatic cleavage, fluorescent labeling and high-performance liquid chromatography (HPLC) analysis demonstrated a peak consistent with Gal-beta-(1-->3)-GalNAc, with similar MS/MS fragmentation. Additionally, upon chemical analysis, a GlcNAc-containing O-linked carbohydrate moiety was discovered. Protein blotting with anti-O-GlcNAc antibody (clone CTD110.6) was positive in a subpopulation of the 14kDa alcohol-soluble protein fraction, but a hot capping experiment was negative. Therefore, the GlcNAc residue in this case is unlikely to be terminal. Additionally, a positive reaction with CTD110.6mAb cannot be taken as absolute proof of O-GlcNAc modification and further confirmatory experiments should be employed. We hypothesize that O-glycosylation may contribute to protein functionality or regulation. Further investigation is required to identify the specific proteins with these modifications. This 'reverse' approach could lead to the identification of proteins involved in mRNA targeting, signaling, translation, anchoring or maintenance of translational quiescence and may be applied to germinating rice seed extracts for further elucidation of protein function and regulation. 相似文献
80.
Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective
of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available
in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry
(XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot stage
microscopy, scanning electron microscopy), contact angle, and intrinsic dissolution rate (IDR). All crystalline ATC samples
were found to be stable form I, however one sample possessed polymorphic impurity, evidenced in XRPD and DSC analysis. Amongst
the amorphous ATC samples, XRPD demonstrated five samples to be amorphous ‘form 27’, while, one matched amorphous ‘form 23’.
Thermal behavior of amorphous ATC samples was compared to amorphous ATC generated by melt quenching in DSC. ATC was found
to be an excellent glass former with Tg/Tm of 0.95. Residual crystallinity was detected in two of the amorphous samples by complementary use of conventional and modulated
DSC techniques. The wettability and IDR of all amorphous samples was found to be higher than the crystalline samples. In conclusion,
commercial ATC samples exhibited diverse solid state behavior that can impact the performance and stability of the dosage
forms. 相似文献