The mechanisms of cancer cell adaptation to tumor microenvironmental conditions, such as hypoxia and nutrient starvation, are currently receiving much attention as possible therapeutic targets. In an attempt to identify selectively cytotoxic substances against cancer cells adapted to nutrient starvation, 4 abietane-type diterpenes, sugiol (1), 6-α-hydroxysugiol (2), cryptojaponol (3), and 6-hydroxy- 5,6-dehydrosugiol (4), were isolated from the bark of Taxodium distichum L. Rich var. distichum (bald cypress). Compounds 1, 2, and 4 showed potent cytotoxic activity against PANC-1 cells adapted to nutrient-starved conditions with half-maximal effective concentration (EC50) values of 6.4-9.2 μM, whereas the EC50 values of these compounds against PANC-1 cells under general culture conditions were more than 100 μM. Alternatively, compound 3, which we report for the first time in the genus Taxodium, showed moderate cytotoxicity against PANC-1 cells under nutrient-starved conditions with an EC50 of 37.9 μM. The selective index (S.I.), which compared the activity under nutrient-starved conditions with that under general culture conditions, was low (7.9). Further investigation revealed that the selective cytotoxic activity of compound 2 might be affecting the mitochondria.

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3b-hydroxyeuparin 3-Oglucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-b-D-glucoside (2), and isorhamentin 3-O-b-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 lM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3b-hydroxyeuparin 3-Oglucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-b-D-glucoside (2), and isorhamentin 3-O-b-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 lM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3b-hydroxyeuparin 3-Oglucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-b-D-glucoside (2), and isorhamentin 3-O-b-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 lM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.

Based on our previous work with “pseudostationary-ion exchanger sweeping”, we use this strategy to develop a sensitive, reliable and robust method for the analysis of the newly-FDA approved hepatitis C antiviral drugs namely; sofosbuvir (SOV), daclatasvir (DAC), ledipasvir (LED) and velpatasvir (VEP) in their pure forms and co-formulated pharmaceutical dosage forms using micellar electrokinetic chromatography (MEKC) as a separation method. For the first time, a successful separation of all the investigated compounds was achieved in less than 8 min using a basic background electrolyte (BGE) composed of 25 mmol L−1 SDS + 20% (v/v) ACN (acetonitrile) in 10 mmol L−1 disodium tetraborate buffer (final apparent pH is 9.90). A special focus was given to optimize the composition of the sample matrix to maintain the solubility of the analytes within the sample zone while gaining additional benefits regarding analyte zone focusing. It was found that replacing phosphoric acid (as a sample matrix) with a zwitterionic/isoelectric buffering compound (L-glutamic acid) has a substantial positive impact on the obtained enrichment efficiency. The interplay of other enrichment principles such as the retention factor gradient effect (RFGE) is also discussed. A full validation study is performed based on the pharmacopeial and ICH guidelines. The obtained limits of detection and quantitation are as low as 0.63 and 1.3 μg mL−1; respectively for SOV and DAC and 1.3 and 2.5 μg mL−1; respectively for LED and VEP using UV-DAD as a detection method. The selectivity of the developed method for determination of the studied compounds in their pharmaceutical dosage forms or in the presence of ribavirin (RIB) or elbasvir (ELB), which are other prescribed medications in the treatment regimen of patients with hepatitis C virus infection, is demonstrated. It is shown that with acidic sample matrix and basic BGE, an efficient and precise approach was designed in which analyte adsorption on the capillary wall was minimized while keeping repeatable peak height, peak area and migration time together with the highest possible enrichment efficiency.

This study tests the hypothesis that association complexes formed between enoxaparin and cetyltrimethylammonium bromide (CTAB) augment permeation across the gastrointestional mucosa due to improved encapsulation of this hydrophilic macromolecule within biocompatible poly (lactide-co-glycolide, PLGA RG 503) nanoparticles. When compared to free enoxaparin, association with CTAB increased drug encapsulation efficiency within PLGA nanoparticles from 40.3 ± 3.4% to 99.1 ± 1.0%. Drug-release from enoxaparin/CTAB PLGA nanoparticles was assessed in HBSS, pH 7.4 and in FASSIFV2, pH 6.5, suggesting effective protection of PLGA-encapsulated enoxaparin from unfavorable intestinal conditions. Stability of enoxaparin/CTAB ion pair complex was pH-dependent, resulting in more rapid dissociation under simulated plasma conditions (i.e., pH 7.4) than in the presence of a mild acidic gastrointestinal environment (i.e., pH 6.5). Intestinal flux of enoxaparin complexes across in vitro Caco-2 cell monolayers was greater when encapsulated within PLGA nanoparticles. Limited changes in transepithelial transport of PLGA-encapsulated enoxaparin complexes in the presence of increasing CTAB concentrations suggests significant contribution of size-dependent passive diffusion as the predominant transport mechanism facilitating intestinal absorption.

This study tests the hypothesis that association complexes formed between enoxaparin and cetyltrimethylammonium bromide (CTAB) augment permeation across the gastrointestional mucosa due to improved encapsulation of this hydrophilic macromolecule within biocompatible poly (lactide-co-glycolide, PLGA RG 503) nanoparticles. When compared to free enoxaparin, association with CTAB increased drug encapsulation efficiency within PLGA nanoparticles from 40.3 ± 3.4% to 99.1 ± 1.0%. Drug-release from enoxaparin/CTAB PLGA nanoparticles was assessed in HBSS, pH 7.4 and in FASSIFV2, pH 6.5, suggesting effective protection of PLGA-encapsulated enoxaparin from unfavorable intestinal conditions. Stability of enoxaparin/CTAB ion pair complex was pH-dependent, resulting in more rapid dissociation under simulated plasma conditions (i.e., pH 7.4) than in the presence of a mild acidic gastrointestinal environment (i.e., pH 6.5). Intestinal flux of enoxaparin complexes across in vitro Caco-2 cell monolayers was greater when encapsulated within PLGA nanoparticles. Limited changes in transepithelial transport of PLGA-encapsulated enoxaparin complexes in the presence of increasing CTAB concentrations suggests significant contribution of size-dependent passive diffusion as the predominant transport mechanism facilitating intestinal absorption.

This study tests the hypothesis that association complexes formed between enoxaparin and cetyltrimethylammonium bromide (CTAB) augment permeation across the gastrointestional mucosa due to improved encapsulation of this hydrophilic macromolecule within biocompatible poly (lactide-co-glycolide, PLGA RG 503) nanoparticles. When compared to free enoxaparin, association with CTAB increased drug encapsulation efficiency within PLGA nanoparticles from 40.3 ± 3.4% to 99.1 ± 1.0%. Drug-release from enoxaparin/CTAB PLGA nanoparticles was assessed in HBSS, pH 7.4 and in FASSIFV2, pH 6.5, suggesting effective protection of PLGA-encapsulated enoxaparin from unfavorable intestinal conditions. Stability of enoxaparin/CTAB ion pair complex was pH-dependent, resulting in more rapid dissociation under simulated plasma conditions (i.e., pH 7.4) than in the presence of a mild acidic gastrointestinal environment (i.e., pH 6.5). Intestinal flux of enoxaparin complexes across in vitro Caco-2 cell monolayers was greater when encapsulated within PLGA nanoparticles. Limited changes in transepithelial transport of PLGA-encapsulated enoxaparin complexes in the presence of increasing CTAB concentrations suggests significant contribution of size-dependent passive diffusion as the predominant transport mechanism facilitating intestinal absorption.

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