The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Christopher J H Porter - One of the best experts on this subject based on the ideXlab platform.
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Lipids in the stomach implications for the evaluation of Food effects on oral drug absorption
Pharmaceutical Research, 2018Co-Authors: Frederic Carriere, Mirko Koziolek, Christopher J H PorterAbstract:Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of Food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with Lipids, including Lipids in Food, and is commonly explained by the ability of Lipids to enhance drug solubility in intestinal luminal fluids. in contrast, the impact of Lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of Lipids in the gastrointestinal tract. The stomach therefore acts to ‘pre-process’ Lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. in this article, the mechanisms by which Lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of Lipids and their application to better understand Food effects on drug release and absorption.
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intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation
Molecular Pharmaceutics, 2013Co-Authors: Yan Yan Yeap, Natalie L Trevaskis, Tim Quach, William N Charman, Christopher J H PorterAbstract:The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by coadministration with Lipids in Food or lipid-based oral formulations. Coadministration with Lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phases remain poorly understood. Classically, drug absorption is believed to be a product of the drug concentration in free solution and the apparent permeability across the absorptive membrane. Solubilization in colloidal phases such as mixed micelles increases dissolution rate and total solubilized drug concentrations, but does not directly enhance (and may reduce) the free drug concentration. in the absence of changes to cellular permeability (which is often high for lipophilic, PWSD), significant changes to membrane flux are therefore unexpected. Realizing that increases in effective dissolution rate may be a significant driver of increases in drug absorption for P...
Junhu Zhou - One of the best experts on this subject based on the ideXlab platform.
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inhibition of n vanillylnonanamide in anaerobic digestion of Lipids in Food waste microorganisms damage and blocked electron transfer
Journal of Hazardous Materials, 2020Co-Authors: Jun Cheng, Haihua Zhang, Luyun Yuan, Haiquan Dong, Yuyou Li, Junhu ZhouAbstract:Abstract To study the inhibited degradation metabolism and anaerobic digestion of typical Lipids in Food waste, an artificially produced capsaicin, N-Vanillylnonanamide, a typical soluble component in waste Lipids, was added to a glycerol trioleate anaerobic digestion system. The microorganisms damage and blocked electron transfer caused by N-Vanillylnonanamide during anaerobic digestion were further clarified. Scanning electron microscopy and transmission electron microscopy images demonstrated that N-Vanillylnonanamide (≥4 wt%) structurally damaged microorganisms via cell membrane breakage, which impair their function. N-Vanillylnonanamide inhibited the activities of the key enzyme CoA, AK, F420, and CoM, which are relevant for both degradation metabolism and anaerobic digestion. 16S rRNA analysis showed that dominant bacterial and archaeal communities markedly decreased after anaerobic digestion of glycerol trioleate with N-Vanillylnonanamide (≥4 wt%). For example, the proportion of Methanosarcina decreased from 30 % to 6 %. Current-voltage curves indicated that the electron transfer rate in the community of microorganisms decreased by 99 % from 4.67 × 10−2 to 5.66 × 10−4 s−1 in response to N-Vanillylnonanamide (40 wt%). The methane yield during anaerobic digestion of glycerol trioleate decreased by 84.0 % from 780.21–142.10 mL/g-total volatile solids with N-Vanillylnonanamide (40 wt%).
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Hydrothermal alkali pretreatment contributes to fermentative methane production of a typical lipid from Food waste through co-production of hydrogen with methane
Bioresource Technology, 2020Co-Authors: Jun Cheng, Haiquan Dong, Junhu Zhou, Yuyou LiAbstract:Abstract in order to relieve the suppression problems of methanogenesis with microorganisms surrounded by undegraded Lipids in Food waste, hydrothermal alkali pretreatment was utilized to degrade Lipids for promoted methane production through the co-production process of hydrogen with methane. GC–MS results demonstrated that oleic acids and hexadecanoic acids derived from degraded glycerol trioleate increased (from 43.29% to 58.22%, and from 1.06% to 8.25%, respectively) when the pretreatment temperature was increased from 160 °C to 220 °C. SEM, TEM and FTIR analyses showed that the pre-treatment at 220 °C effectively degraded 87.56% of glycerol trioleate and drastically relieved the covering of methanogens by non-degraded Lipids. The methane yield and the production peak rate of glycerol trioleate also increased (from 636.85 to 877.47 mL CH4/g-total volatile solid (VS), and from 32.60 to 51.22 mL CH4/g-VS/d, respectively), which led to an increased energy conversion efficiency from 48.05% to 66.21% through the co-production of hydrogen with methane.
Yan Yan Yeap - One of the best experts on this subject based on the ideXlab platform.
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Supersaturation as a driving force for drug absorption from colloidal lipid species in the intestine
2020Co-Authors: Yan Yan YeapAbstract:This thesis seeks to elucidate the mechanism of drug absorption from the colloidal micellar and vesicular species that form in the gastrointestinal (GI) tract during lipid digestion. in addition to absorption from the free fraction of drug molecules that exist in equilibrium with drug solubilised in the colloidal reservoir, two alternative models of drug absorption were explored: (i) collisional drug absorption where lipid colloidal phases interact directly with the absorptive membrane, and (ii) supersaturation-enhanced absorption where transient changes to colloid structure and content in situ lead to drug supersaturation, thereby boosting drug thermodynamic activity and rendering solubilised drug more available for absorption via the free fraction. Collisional drug absorption was explored by comparing the intestinal absorptive flux of cinnarizine (Cin) from two distinctly different colloids (micelles vs. vesicles) that were matched for Cin solubilisation capacity and drug loading (and therefore thermodynamic activity). in these systems the number of micellar particles was substantially higher than that of vesicles, and as such collisional absorption of Cin was expected to be higher from micelles. The absorption of Cin from micelles and vesicles, however, was not statistically different, suggesting little collisional involvement in drug absorption. Receptor-mediated collisional absorption was examined by assessing Cin bioavailability from a lipid emulsion in the absence and presence of inhibitors of common lipid uptake transporters (e.g. SR-BI, CD36, NPC1L1). Cin bioavailability was unchanged by inhibitor co-administration. Collectively, the data suggest that collision-mediated uptake is not a significant driver for drug absorption from intestinal lipid colloidal phases, and that drug absorption occurs largely from the free fraction. Subsequently, attention turned to the possibility that drug supersaturation might be stimulated during endogenous processing of intestinal lipid colloidal phases. Two mechanisms were investigated: (i) interaction of lipid colloidal phases with bile secretions, where bile-induced changes to colloid microstructure may lead to reductions in drug solubilisation capacity and (ii) lipid absorption from intestinal colloids, where reductions in colloidal lipid content may reduce drug solubilisation capacity at the intestinal unstirred water layer (UWL). The addition of donor rat bile to Cin-loaded colloids (Cin was loaded at sub-saturated concentrations) resulted in a decrease in Cin solubilisation and the generation of Cin supersaturation. Bile-induced supersaturation was subsequently shown to increase the intestinal absorptive flux and systemic exposure of Cin from both medium-chain and long-chain lipid containing colloids. To assess the potential for lipid absorption to induce drug supersaturation, the intestinal absorptive flux of Cin from oleic acid-containing colloids was assessed under conditions of normal lipid absorption vs. inhibited lipid absorption (oleic acid absorption was inhibited by co-administration of amiloride, an inhibitor of UWL acidity). When oleic acid absorption was suppressed, the absorption of Cin was dramatically attenuated. Assessment of Cin solubilisation behaviour under conditions that simulate lipid absorption at the UWL subsequently indicated that supersaturation was likely to be responsible for the enhanced Cin absorption observed during normal lipid absorption. in summary, supersaturation appears to be an important driving force for drug absorption from lipid-based intestinal colloids. Two novel mechanisms have been identified by which drug supersaturation may be naturally triggered in the small intestine (bile dilution and lipid absorption). The findings enhance mechanistic understanding of the effects of Lipids in Food or formulations on drug absorption and are expected to inform the development of more rational design criteria for LBF.
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intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation
Molecular Pharmaceutics, 2013Co-Authors: Yan Yan Yeap, Natalie L Trevaskis, Tim Quach, William N Charman, Christopher J H PorterAbstract:The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by coadministration with Lipids in Food or lipid-based oral formulations. Coadministration with Lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phases remain poorly understood. Classically, drug absorption is believed to be a product of the drug concentration in free solution and the apparent permeability across the absorptive membrane. Solubilization in colloidal phases such as mixed micelles increases dissolution rate and total solubilized drug concentrations, but does not directly enhance (and may reduce) the free drug concentration. in the absence of changes to cellular permeability (which is often high for lipophilic, PWSD), significant changes to membrane flux are therefore unexpected. Realizing that increases in effective dissolution rate may be a significant driver of increases in drug absorption for P...
Jun Cheng - One of the best experts on this subject based on the ideXlab platform.
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inhibition of n vanillylnonanamide in anaerobic digestion of Lipids in Food waste microorganisms damage and blocked electron transfer
Journal of Hazardous Materials, 2020Co-Authors: Jun Cheng, Haihua Zhang, Luyun Yuan, Haiquan Dong, Yuyou Li, Junhu ZhouAbstract:Abstract To study the inhibited degradation metabolism and anaerobic digestion of typical Lipids in Food waste, an artificially produced capsaicin, N-Vanillylnonanamide, a typical soluble component in waste Lipids, was added to a glycerol trioleate anaerobic digestion system. The microorganisms damage and blocked electron transfer caused by N-Vanillylnonanamide during anaerobic digestion were further clarified. Scanning electron microscopy and transmission electron microscopy images demonstrated that N-Vanillylnonanamide (≥4 wt%) structurally damaged microorganisms via cell membrane breakage, which impair their function. N-Vanillylnonanamide inhibited the activities of the key enzyme CoA, AK, F420, and CoM, which are relevant for both degradation metabolism and anaerobic digestion. 16S rRNA analysis showed that dominant bacterial and archaeal communities markedly decreased after anaerobic digestion of glycerol trioleate with N-Vanillylnonanamide (≥4 wt%). For example, the proportion of Methanosarcina decreased from 30 % to 6 %. Current-voltage curves indicated that the electron transfer rate in the community of microorganisms decreased by 99 % from 4.67 × 10−2 to 5.66 × 10−4 s−1 in response to N-Vanillylnonanamide (40 wt%). The methane yield during anaerobic digestion of glycerol trioleate decreased by 84.0 % from 780.21–142.10 mL/g-total volatile solids with N-Vanillylnonanamide (40 wt%).
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Hydrothermal alkali pretreatment contributes to fermentative methane production of a typical lipid from Food waste through co-production of hydrogen with methane
Bioresource Technology, 2020Co-Authors: Jun Cheng, Haiquan Dong, Junhu Zhou, Yuyou LiAbstract:Abstract in order to relieve the suppression problems of methanogenesis with microorganisms surrounded by undegraded Lipids in Food waste, hydrothermal alkali pretreatment was utilized to degrade Lipids for promoted methane production through the co-production process of hydrogen with methane. GC–MS results demonstrated that oleic acids and hexadecanoic acids derived from degraded glycerol trioleate increased (from 43.29% to 58.22%, and from 1.06% to 8.25%, respectively) when the pretreatment temperature was increased from 160 °C to 220 °C. SEM, TEM and FTIR analyses showed that the pre-treatment at 220 °C effectively degraded 87.56% of glycerol trioleate and drastically relieved the covering of methanogens by non-degraded Lipids. The methane yield and the production peak rate of glycerol trioleate also increased (from 636.85 to 877.47 mL CH4/g-total volatile solid (VS), and from 32.60 to 51.22 mL CH4/g-VS/d, respectively), which led to an increased energy conversion efficiency from 48.05% to 66.21% through the co-production of hydrogen with methane.
Yuyou Li - One of the best experts on this subject based on the ideXlab platform.
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inhibition of n vanillylnonanamide in anaerobic digestion of Lipids in Food waste microorganisms damage and blocked electron transfer
Journal of Hazardous Materials, 2020Co-Authors: Jun Cheng, Haihua Zhang, Luyun Yuan, Haiquan Dong, Yuyou Li, Junhu ZhouAbstract:Abstract To study the inhibited degradation metabolism and anaerobic digestion of typical Lipids in Food waste, an artificially produced capsaicin, N-Vanillylnonanamide, a typical soluble component in waste Lipids, was added to a glycerol trioleate anaerobic digestion system. The microorganisms damage and blocked electron transfer caused by N-Vanillylnonanamide during anaerobic digestion were further clarified. Scanning electron microscopy and transmission electron microscopy images demonstrated that N-Vanillylnonanamide (≥4 wt%) structurally damaged microorganisms via cell membrane breakage, which impair their function. N-Vanillylnonanamide inhibited the activities of the key enzyme CoA, AK, F420, and CoM, which are relevant for both degradation metabolism and anaerobic digestion. 16S rRNA analysis showed that dominant bacterial and archaeal communities markedly decreased after anaerobic digestion of glycerol trioleate with N-Vanillylnonanamide (≥4 wt%). For example, the proportion of Methanosarcina decreased from 30 % to 6 %. Current-voltage curves indicated that the electron transfer rate in the community of microorganisms decreased by 99 % from 4.67 × 10−2 to 5.66 × 10−4 s−1 in response to N-Vanillylnonanamide (40 wt%). The methane yield during anaerobic digestion of glycerol trioleate decreased by 84.0 % from 780.21–142.10 mL/g-total volatile solids with N-Vanillylnonanamide (40 wt%).
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Hydrothermal alkali pretreatment contributes to fermentative methane production of a typical lipid from Food waste through co-production of hydrogen with methane
Bioresource Technology, 2020Co-Authors: Jun Cheng, Haiquan Dong, Junhu Zhou, Yuyou LiAbstract:Abstract in order to relieve the suppression problems of methanogenesis with microorganisms surrounded by undegraded Lipids in Food waste, hydrothermal alkali pretreatment was utilized to degrade Lipids for promoted methane production through the co-production process of hydrogen with methane. GC–MS results demonstrated that oleic acids and hexadecanoic acids derived from degraded glycerol trioleate increased (from 43.29% to 58.22%, and from 1.06% to 8.25%, respectively) when the pretreatment temperature was increased from 160 °C to 220 °C. SEM, TEM and FTIR analyses showed that the pre-treatment at 220 °C effectively degraded 87.56% of glycerol trioleate and drastically relieved the covering of methanogens by non-degraded Lipids. The methane yield and the production peak rate of glycerol trioleate also increased (from 636.85 to 877.47 mL CH4/g-total volatile solid (VS), and from 32.60 to 51.22 mL CH4/g-VS/d, respectively), which led to an increased energy conversion efficiency from 48.05% to 66.21% through the co-production of hydrogen with methane.