Administration of resveratrol: What formulation solutions to bioavailability limitations?

Amri, A.; Chaumeil, Jean‐Claude; Sfar, Souad; Charrueau, Christine

doi:10.1016/j.jconrel.2011.09.083

Cited by 535 publications

(428 citation statements)

References 84 publications

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“…Much higher values of the absorptivity parameters from OPT formulation can be ascribed to the transport of drug via lymphatic pathways, in accordance with an earlier literature report (Sun et al, 2011). The existence of enterohepatic circulation and extensive first-pass metabolism by CYP3A4 in liver has been documented as the plausible cause for low oral bioavailability of t-RVT (Marier et al, 2002;Amri et al, 2012). Marked enhancement in the effective permeability, a direct measure of absorption across the intestine (Bandyopadhyay et al, 2012), of the SNEDDS clearly demonstrates that the OPT formulation was able to augment drug absorption in rat.…”

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

“…trans-resveratrol (t-RVT), chosen in the present study is a BCS class II drug with poor water-solubility and high permeability (log P of 3.1) (Amri et al, 2012). Besides these, it undergoes rapid first-pass metabolism by CYP3A4 in the liver and suffers enterohepatic recirculation (Marier et al, 2002;, leading eventually to marked reduction in the drug oral bioavailable fraction (almost zero) in humans and animals like rats (Amri et al, 2012). Under the aforementioned circumstances, various formulation approaches of t-RVT have been reported, such as liposome (Hung et al, 2006), solid dispersions (Wegiel et al, 2013), b-cyclodextrins inclusion complex (TrochePesqueira et al, 2013), microspheres (Nam et al, 2005), suspensions, but all with limited fruition.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics andin situsingle pass intestinal perfusion (SPIP) studies

2014

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Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X 1 ) and surfactant (X 2 ) as the critical factor variables. The SNEDDS were optimized using 3 2 central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of K a (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT. KeywordsBioavailability, central composite design, in situ single pass intestinal perfusion, pharmacokinetic study, self-nanoemulsifying drug-delivery system History

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics andin situsingle pass intestinal perfusion (SPIP) studies

2014

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“…A likely explanation of such discrepancies would be the differences in the dose and the route of administration. Resveratrol pharmacokinetics have been extensively studied, revealing that enteric absorption is up to 80 % after oral administration, while up to 98 % of the compound is excreted 7-15 h after administration [55]. Accordingly, resveratrol treatment should be performed either dietary at high doses or intraperitoneally but with more frequent injections than made in the abovementioned studies.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

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Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1 G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests.We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1 G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1 G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

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“…administration of resveratrol (20 mg/kg) to rats showed maximum plasma concentrations of resveratrol and its metabolites in the range from 2 to 13 M (61). However, a number of studies demonstrated that the poor bioavailability of resveratrol can be enhanced by various methods such as encapsulation with cyclodextrin, formulation with piperine, and incorporation of resveratrol into microparticles, liposomes, nanocapsules, and emulsion (62). For example, oral administration of a single high dose of resveratrol (100 mg/kg) in mice with or without piperine (10 mg/kg) supplementation resulted in a dramatic increase in maximum plasma resveratrol concentration from 10 to 154 M (63).…”

Section: Discussionmentioning

confidence: 99%

Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation

Kwon

Seo

Heo

et al. 2012

Journal of Biological Chemistry

116

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Background: Adipogenesis contributes to the increase in adipose tissue mass. Results: Preadipocytes treated with piceatannol showed reduced adipogenesis with impairment of the early cell cycle progress and insulin-signaling pathway. Conclusion:The anti-adipogenic function of piceatannol is through inhibition of mitotic clonal expansion and insulin receptor activity in the early phase of adipogenesis. Significance: Piceatannol is a novel anti-adipogenic compound that could modulate development of adipose tissue.

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Administration of resveratrol: What formulation solutions to bioavailability limitations?

Cited by 535 publications

References 84 publications

Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics andin situsingle pass intestinal perfusion (SPIP) studies

Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics andin situsingle pass intestinal perfusion (SPIP) studies

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation

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