167 research outputs found
Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery
Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phaseâsolubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 Ă 103 Mâ1 and 4.27 Ă 103 Mâ1. Fourier transforms infrared spectroscopy indicated entrance of an OâCH2 or OCH3âC6H4âOCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3âC6H4âOCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH âź 7.4) was improved by âź10.7-fold and âź21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by âź2-fold and âź3-fold for Red-Br-Nosâβ-CD-GGM and Red-Br-Nosâmethyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nosâβ-CD and Red-Br-Nosâmethyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer
Biodegradable sodium alginate and lignosulphonic acid blends: characterization and swelling studies
Avaliação da Goma Guar no desenvolvimento de comprimidos matriciais de liberação controlada de teofilina
Partner in fat metabolism: role of KLFs in fat burning and reproductive behavior
The abnormalities caused by excess fat accumulation can result in pathological conditions which are linked to several interrelated diseases, such as cardiovascular disease and obesity. This set of conditions, known as metabolic syndrome, is a global pandemic of enormous medical, economic, and social concern affecting a significant portion of the worldâs population. Although genetics, physiology and environmental components play a major role in the onset of disease caused by excessive fat accumulation, little is known about how or to what extent each of these factors contributes to it. The worm, Caenorhabditis elegans offers an opportunity to study disease related to metabolic disorder in a developmental system that provides anatomical and genomic simplicity relative to the vertebrate animals and is an excellent eukaryotic genetic model which enable us to answer the questions concerning fat accumulation which remain unresolved. The stored triglycerides (TG) provide the primary source of energy during periods of food deficiency. In nature, lipid stored as TGs are hydrolyzed into fatty acids which are broken down through β-oxidation to yield acetyl-CoA. Our recent study suggests that a member of C. elegans KrĂźppel-like factor, klf-3 regulates lipid metabolism by promoting FA β-oxidation and in parallel may contribute in normal reproduction and fecundity. Genetic and epigenetic factors that influence this pathway may have considerable impact on fat related diseases in human. Increasing number of studies suggest the role of mammalian KLFs in adipogenesis. This functional conservation should guide our further effort to explore C. elegans as a legitimate model system for studying the role of KLFs in many pathway components of lipid metabolism
Determination of hydroxyl groups in biorefinery resources via quantitative 31P NMR spectroscopy
The analysis of chemical structural characteristics of biorefinery product streams (such as lignin and tannin) has advanced substantially over the past decade, with traditional wet-chemical techniques being replaced or supplemented by NMR methodologies. Quantitative 31P NMR spectroscopy is a promising technique for the analysis of hydroxyl groups because of its unique characterization capability and broad potential applicability across the biorefinery research community. This protocol describes procedures for (i) the preparation/solubilization of lignin and tannin, (ii) the phosphitylation of their hydroxyl groups, (iii) NMR acquisition details, and (iv) the ensuing data analyses and means to precisely calculate the content of the different types of hydroxyl groups. Compared with traditional wet-chemical techniques, the technique of quantitative 31P NMR spectroscopy offers unique advantages in measuring hydroxyl groups in a single spectrum with high signal resolution. The method provides complete quantitative information about the hydroxyl groups with small amounts of sample (~30 mg) within a relatively short experimental time (~30-120 min)
Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms
Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic
properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocininduced
diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative
activities in mice in order to examine possible underlying mechanisms.
Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate
and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot
plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The
antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for
prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain
using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia.
Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide),
palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the
abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole
reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case
test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was
observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME
decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized
by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative
activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static
and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal
latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency.
Conclusions: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The
antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and
GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed
Self-emulsifying therapeutic system: a potential approach for delivery of lipophilic drugs
High Performace Liquid Chromtographic Determination of Nicardipine Hydrochloride in Human Plasma
A sensitive high-performance liquid chromatographic method was developed for the estimation of nicardipine hydrochloride in human plasma. Varying amount of nicardipine hydrochloride (2.5 to 150 ng/0.5 mL) and fixed quantity (100 ng/0.5 mL) of nifedipine (internal standard) was added to blank human plasma, and a single step extraction was carried out with ethyl acetate. The mixture was centrifuged, ethyl acetate layer separated, dried and reconstituted with 100 ÎźL of acetonitrile. Twenty microliters of this solution was injected into a reverse phase C-18 column using a mobile phase consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate (pH 4.0) in the ratio of 60:40 v/v and the eluents were monitored at 239 nm. The method was validated for its linearity, precision and accuracy. The calibration curve was linear in the range of 5-150 ng/0.5 mL of plasma and the lower detection limit was 2.5 ng/0.5 mL of plasma. The intra- and inter-day variation was found to be less than 2.5% indicating that the method is highly precise. The mean recovery of nicardipine hydrochloride from plasma samples was 89.6Âą2.60%. The proposed HPLC method was applied for the estimation of nicardipine hydrochloride in human plasma after oral administration of an immediate release nicardipine hydrochloride capsule (dose 30 mg) to 6 adult male volunteers. There was no interference of either the drug metabolites or other plasma components with the proposed HPLC method for the estimation of nicardipine hydrochloride in human plasma. Due to its simplicity, sensitivity, high precision and accuracy, the proposed HPLC method may be used for biopharmaceutical and pharmacokinetic evaluation of nicardipine hydrochloride and its formulations in human
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