Mechanisms of poor oral bioavailability of flavonoid Morin in rats: From physicochemical to biopharmaceutical evaluations

Li, Jianbo; Yang, Yang; Ning, Erjuan; Peng, Youmei; Zhang, Jinjie

doi:10.1016/j.ejps.2018.12.011

Cited by 40 publications

(31 citation statements)

References 18 publications

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“…As many other drugs, polyphenol absorption occurs mainly in the small intestine [60]; however, in the case of MH, the information about its oral delivery is limited. Nevertheless, pharmacokinetic studies in animal models by different authors have reported that MH absorption occurs mainly in the small intestine and the colon [30,31,61]. Some of these studies suggest that to improve the oral bioavailability of MH, a BCS class IV drug, it is crucial to avoid both efflux and intestinal metabolism.…”

Section: Resultsmentioning

confidence: 99%

“…Morin (3,5,7,2 ,4 -pentahydroxyflavone) (MH) is a flavonoid that commonly occurs in various fruits and vegetables of the Moraceae family [22,23], which has been shown a remarkable antioxidant [24,25], anti-inflammatory [26], neuroprotective [27], and anti-cancer activity [28] in different animal models. Thus, its oral administration could have promising health benefits; however, its applications are limited since morin is a BCS class IV molecule of difficult pharmaceutical formulations [29,30], which has very low oral bioavailability; studies suggest that in order to improve it, the intestinal first-pass effect should be avoided [31]. Nonetheless, selecting MH as a molecule probe to study its release behavior from a nanoantioxidant carrier and evaluating the impact that the surface polyphenolic layer of this nanosystem has on the release mechanism remains a challenge in pharmaceutical interest, which seeks to optimize potential formulations that include these novel nanoantioxidants.…”

Section: Introductionmentioning

confidence: 99%

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Nanoantioxidant–Based Silica Particles as Flavonoid Carrier for Drug Delivery Applications

2020

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Nanosystems used in pharmaceutical formulations have shown promising results in enhancing the administration of drugs of difficult formulations. In particular, porous silica nanoparticles have demonstrated excellent properties for application in biological systems; however, there are still several challenges related to the development of more effective and biocompatible materials. An interesting approach to enhance these nanomaterials has been the development of nanoantioxidant carriers. In this work, a hybrid nanoantioxidant carrier based on porous silica nanoplatform with rosmarinic acid antioxidant immobilized on its surface were developed and characterized. Techniques such as dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), N2 adsorption–desorption measurements, differential scanning calorimetry (DSC), Fourier transform–infrared spectroscopy (FT-IR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH●) assay were used to characterize and evaluate the antioxidant activity of nanocarriers. In addition, drug release profile was evaluated using two biorelevant media. The antioxidant activity of rosmarinic acid was maintained, suggesting the correct disposition of the moiety. Kinetic studies reveal that more morin is released in the simulated intestinal fluid than in the gastric one, while an anomalous non–Fickian release mechanism was observed. These results suggest a promising antioxidant nanocarrier suitable for future application in drug delivery.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoantioxidant–Based Silica Particles as Flavonoid Carrier for Drug Delivery Applications

2020

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“…This suggests that applying appropriate modification of morin dosage form can improve its therapeutic effect on meningitis induced by Listeria infection [35,36]. There are few studies on the stability of morin, but the effect of oral morin is very poor, indicating that the state of oral morin is not stable [37], so intravenous injection may become an important direction for its research and application. Although the oral effect of morin can be greatly improved after some modification, whether it is convenient for large-scale production and development remains to be studied [38].…”

Section: Discussionmentioning

confidence: 99%

Morin inhibits Listeria monocytogenes virulence in vivo and in vitro by targeting listeriolysin O and inflammation

Wang

et al. 2020

Preprint

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Background: Listeria monocytogenes (L. monocytogenes) is a global opportunistic intracellular pathogen that can cause many diseases, including meningitis and abortion in humans and animals; thus, L. monocytogenes poses a great threat to public safety and the development of the aquaculture industry. The pore-forming toxin listeriolysin O (LLO) is one of the most important virulence factors of L. monocytogenes; LLO can promote cytosolic bacterial proliferation and aid in evading the attacks of the host immune system. In addition, L. monocytogenes infection can trigger a series of severe inflammatory reactions.Results: Here, on the basis of our previous studies, we further confirmed that morin lacking anti-Listeria activity could inhibit LLO oligomerization and found that morin could effectively alleviate the inflammation induced by Listeria in vivo and in vitro and has an obvious protective effect on infected cells and mice.Conclusions: Thus, we further prove that morin is a valuable drug precursor to be developed for the treatment of Listeria infection.

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“…Some attempts have been carried out by combination of PC and SNEDDS to enhance oral bioavailability of bioactive compounds or biomacromolecule, such as morin (Zhang et al., 2011, 2015, 2016; Li et al., 2019), akebia saponin D (Shen et al., 2016; Wang et al., 2019), rosuvastatin calcium (Beg et al., 2019), paclitaxel (Ding et al., 2018), curcumin (Shukla et al., 2017), ellagic acid (Avachat & Patel, 2015), baicalin (Wu et al., 2014), matrine (Ruan et al., 2010), and insulin (Zhang et al., 2012). Most of above researches focused on preparation, characterization, bioavailability, or pharmacodynamics of the PC–SNEDDS complex.…”

Section: Introductionmentioning

confidence: 99%

“…Most of above researches focused on preparation, characterization, bioavailability, or pharmacodynamics of the PC–SNEDDS complex. A few reports studied the mechanisms of bioavailability improvement by PC–SNEDDS complex and attributed these effects to increased membrane permeability (Zhang et al., 2015; Wang et al., 2019), P-gp inhibition (Zhang et al., 2015), destroying self-micelles (Wang et al., 2019), and inhibiting the intestinal metabolism (Wang et al., 2019), but the PC–SNEDDS complex could not bypass first-pass metabolism which will compromise the enhancement of oral absorption (Li et al., 2019). In summary, the underlying exact mechanisms on how PC–SNEDDS complex to improve the absorption of drugs remains unclear and needs to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS

et al. 2019

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In the present study, a water insoluble drug named silybin was encapsulated into self-nanoemulsifying drug delivery system (SNEDDS) following the preparation of silybin-phospholipid complex (SB-PC), then several methods were carried out to characterize SB-PC-SNEDDS and elucidate its mechanisms to improve the oral absorption of SB. Using a dynamic in vitro digestion model, the lipolysis of SB-PC-SNEDDS was proved to be mainly related with the property of its lipid excipients. SB-PC-SNEDDS could significantly enhance the transport of SB across Caco-2 cells, which may partly attribute to the increased cell membrane fluidity and the loss of tight junction according to the analysis results of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and tight junction protein (ZO-1). The result of in situ perfusion showed the intestinal absorption of SB from high to low was SB-PC-SNEDDS, SB-PC, and SB. The extent of lymphatic transport of SB-PC and SB-PC-SNEDDS via the mesenteric duct was 12.2 and 22.7 folds of that of SB, respectively. In the lymph duct cannulated rats, the relative bioavailability (Fr) of SB-PC and SB-PC-SEDDS compared to SB was 1265.9% and 1802.5%, respectively. All the above results provided mechanistic support for oral absorption improvement of water insoluble drugs by the combination of PC and SNEDDS.

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Mechanisms of poor oral bioavailability of flavonoid Morin in rats: From physicochemical to biopharmaceutical evaluations

Cited by 40 publications

References 18 publications

Nanoantioxidant–Based Silica Particles as Flavonoid Carrier for Drug Delivery Applications

Nanoantioxidant–Based Silica Particles as Flavonoid Carrier for Drug Delivery Applications

Morin inhibits Listeria monocytogenes virulence in vivo and in vitro by targeting listeriolysin O and inflammation

Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS

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