Evaluation of a Yeast Hydrolysate from a Novel Strain of Saccharomyces cerevisiae for Mycotoxin Mitigation using In Vitro and In Vivo Models

Mycotoxicoses in animals are caused by exposure to mycotoxin-contaminated feeds. Disease risk is managed using dietary adsorbing agents which reduce oral bioavailability. The objective of this work was to evaluate the efficacy of three selected yeast products as mycotoxin binders using in vitro and in vivo models. Their capacity to adsorb deoxynivalenol (DON), zearalenone (ZEA), and ochratoxin A (OTA) was evaluated using an in vitro model designed to simulate the pH conditions during gastric passage in a monogastric animal. Results showed that only one product, an enzymatic yeast hydrolysate (YHY) of a novel strain Saccharomyces cerevisiae, adsorbed about 45% of DON in solution. Next, we determined the effect of YHY on oral absorption of a DON, ZEA, and OTA mixture using a toxicokinetic model in swine. Toxicokinetic modeling of the plasma concentration-time profiles of DON, OTA, and zearalenone-glucuronide (ZEA-GlcA) showed that YHY tended to reduce the maximal plasma concentration of OTA by 17%. YHY did not reduce oral bioavailability of OTA, DON, and ZEA-GlcA. Within the context of this experiment, and despite some positive indications from both the in vitro and in vivo models employed, we conclude that the YHY prototype was not an effective agent for multiple mycotoxin adsorption.

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LC478, a Novel Di-Substituted Adamantyl Derivative, Enhances the Oral Bioavailability of Docetaxel in Rats

Pharmaceutics ◽

10.3390/pharmaceutics11030135 ◽

2019 ◽

Vol 11 (3) ◽

pp. 135 ◽

Cited By ~ 1

Author(s):

Seung Han ◽

Qili Lu ◽

Kyeong Lee ◽

Young Choi

Keyword(s):

Oral Bioavailability ◽

Oral Absorption ◽

Ussing Chamber ◽

Absolute Bioavailability ◽

Time Curve ◽

Glycoprotein P ◽

Dose Concentration ◽

Chamber Studies

P-glycoprotein (P-gp)-mediated efflux of docetaxel in the gastrointestinal tract mainly impedes its oral chemotherapy. Recently, LC478, a novel di-substituted adamantyl derivative, was identified as a non-cytotoxic P-gp inhibitor in vitro. Here, we assessed whether LC478 enhances the oral bioavailability of docetaxel in vitro and in vivo. LC478 inhibited P-gp mediated efflux of docetaxel in Caco-2 cells. In addition, 100 mg/kg of LC478 increased intestinal absorption of docetaxel, which led to an increase in area under plasma concentration-time curve (AUC) and absolute bioavailability of docetaxel in rats. According to U.S. FDA criteria (I, an inhibitor concentration in vivo tissue)/(IC50, inhibitory constant in vitro) >10 determines P-gp inhibition between in vitro and in vivo. The values 15.6–20.5, from (LC478 concentration in intestine, 9.37–12.3 μM)/(IC50 of LC478 on P-gp inhibition in Caco-2 cell, 0.601 μM) suggested that 100 mg/kg of LC478 sufficiently inhibited P-gp to enhance oral absorption of docetaxel. Moreover, LC478 inhibited P-gp mediated efflux of docetaxel in the ussing chamber studies using rat small intestines. Our study demonstrated that the feasibility of LC478 as an ideal enhancer of docetaxel bioavailability by P-gp inhibition in dose (concentration)-dependent manners.

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Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate

Pharmaceutics ◽

10.3390/pharmaceutics11030107 ◽

2019 ◽

Vol 11 (3) ◽

pp. 107 ◽

Cited By ~ 6

Author(s):

Huiyun Zhang ◽

Qilong Wang ◽

Congyong Sun ◽

Yuan Zhu ◽

Qiuxuan Yang ◽

...

Keyword(s):

Linoleic Acid ◽

Oral Bioavailability ◽

Water Solubility ◽

Oral Absorption ◽

Treatment Effectiveness ◽

Hepatoprotective Effect ◽

Nanoprecipitation Method ◽

Acid Conjugate

：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol’s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2–fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.

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INVESTIGATION OF SOLUBILITY ENHANCEMENT OF PRASUGREL HYDROCHLORIDE: NANOSUSPENSIONS AND CYCLODEXTRIN INCLUSION COMPLEXES

INDIAN DRUGS ◽

10.53879/id.51.02.p0029 ◽

2014 ◽

Vol 51 (02) ◽

pp. 29-38

Author(s):

R. K Devara ◽

◽

P. Reddipogu ◽

S Kumar ◽

B. Rambabu ◽

...

Keyword(s):

Dissolution Rate ◽

Inclusion Complexes ◽

Oral Bioavailability ◽

Oral Absorption ◽

In Vitro Dissolution ◽

Precipitation Method ◽

Formulation Development ◽

Pure Drug

The objective of this study was to investigate nanosuspensions, hydroxypropyl-β-cyclodextrin (HPβCD) complexes and SLS powders for enhancing the solubility and dissolution rate of Prasugrel HCl (PHCl) so as to reduce the fluctuations in its oral bioavailability. PHCl nanosuspensions were prepared using evaporative precipitation method. HPβCD inclusion complexes of PHCl were prepared using physical mixture, co-evaporation and kneading methods. Powders of the pure drug with different SLS amounts were prepared. The formulations were characterized using techniques such as powder x-ray diffractometry, scanning electron microscopy, in vitro dissolution and in vivo absorption in rats. To further aid in the betterment of development of nevirapine nanosuspension, in vitro in vivo correlation (IVIVC) was established using deconvolution technique. Nanosuspensions and HPβCD inclusion complexes of PHCl were successfully prepared. The dissolution rate and oral absorption of PHCl in the form of nanosuspensions was significantly higher than that of HPβCD complexes, SLS powders as well as pure drug. All the techniques investigated in this study can be used to enhance dissolution rate and oral absorption of prasugrel HCl and thus can reduce the fluctuations in its oral bioavailability. Nanosuspensions demonstrated to be better and superior technique when compared to other techniques investigated in enhancing oral bioavailability of PHCl. IVIVC that could aid in further formulation development of PHCl nanosuspension was successfully developed using a deconvolution approach.

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Viscoelastic Emulsion Improved the Bioaccessibility and Oral Bioavailability of Crystalline Compound: A Mechanistic Study Using in Vitro and in Vivo Models

Molecular Pharmaceutics ◽

10.1021/mp5007322 ◽

2015 ◽

Vol 12 (7) ◽

pp. 2229-2236 ◽

Cited By ~ 28

Author(s):

Yuwen Ting ◽

Yike Jiang ◽

Yaqi Lan ◽

Chunxin Xia ◽

Zhenyu Lin ◽

...

Keyword(s):

Oral Bioavailability ◽

Mechanistic Study ◽

Crystalline Compound ◽

In Vivo Models ◽

Compound A

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Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects

Pharmaceutics ◽

10.3390/pharmaceutics13020175 ◽

2021 ◽

Vol 13 (2) ◽

pp. 175

Author(s):

Dong-Gyun Han ◽

Eunju Cha ◽

Jeongmin Joo ◽

Ji Sun Hwang ◽

Sanghyun Kim ◽

...

Keyword(s):

Oral Bioavailability ◽

Oral Absorption ◽

Systematic Investigation ◽

Therapeutic Effects ◽

Poor Solubility ◽

The Poor ◽

Acacia Honey ◽

Biopharmaceutical Properties

Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.

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Assessment of In Vitro Bioaccessibility and In Vivo Oral Bioavailability as Complementary Tools to Better Understand the Effect of Cooking on Methylmercury, Arsenic, and Selenium in Tuna

Toxics ◽

10.3390/toxics9020027 ◽

2021 ◽

Vol 9 (2) ◽

pp. 27

Author(s):

Tania Charette ◽

Danyel Bueno Dalto ◽

Maikel Rosabal ◽

J. Jacques Matte ◽

Marc Amyot

Keyword(s):

Oral Bioavailability ◽

Fish Muscle ◽

In Vitro Models ◽

In Vivo Studies ◽

In Vivo Models ◽

Exposure Pathway ◽

In Vitro Bioaccessibility ◽

Kinetics Of

Fish consumption is the main exposure pathway of the neurotoxicant methylmercury (MeHg) in humans. The risk associated with exposure to MeHg may be modified by its interactions with selenium (Se) and arsenic (As). In vitro bioaccessibility studies have demonstrated that cooking the fish muscle decreases MeHg solubility markedly and, as a consequence, its potential absorption by the consumer. However, this phenomenon has yet to be validated by in vivo models. Our study aimed to test whether MeHg bioaccessibility can be used as a surrogate to assess the effect of cooking on MeHg in vivo availability. We fed pigs raw and cooked tuna meals and collected blood samples from catheters in the portal vein and carotid artery at: 0, 30, 60, 90, 120, 180, 240, 300, 360, 420, 480 and 540 min post-meal. In contrast to in vitro models, pig oral bioavailability of MeHg was not affected by cooking, although the MeHg kinetics of absorption was faster for the cooked meal than for the raw meal. We conclude that bioaccessibility should not be readily used as a direct surrogate for in vivo studies and that, in contrast with the in vitro results, the cooking of fish muscle did not decrease the exposure of the consumer to MeHg.

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