Development of nobiletin–methyl hesperidin amorphous solid dispersion: Novel application of methyl hesperidin as an excipient for hot-melt extrusion

Iwashita, Masazumi; Hashizume, Kohjiro; Umehara, Masaaki; Ishigami, Takaaki; Onishi, Shintaro; Yamamoto, Masaki; Higashi, Kenjirou; Moribe, Kunikazu

doi:10.1016/j.ijpharm.2018.12.092

Cited by 15 publications

(11 citation statements)

References 44 publications

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“…In patent US20190183852A1 assigned to Kao Corp., nobiletin composition with high water solubility was mixed with hesperidin derivative to develop SD. In this patent, a nobiletin containing composition was produced (Iwashita et al., 2019 ). In patent US10391103B2 assigned to Sinotherapeutics Inc., ferroporphyrin SD was developed with a carrier in the ratio of 1:1 to 1:10.…”

Section: Patents On Sdmentioning

confidence: 99%

RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents

et al. 2020

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In the last few decades, solid dispersion (SD) technology had been studied as an approach to produce an amorphous carrier to enhance the solubility, dissolution rate, and bioavailability of poorly water-soluble drugs. The use of suitable carrier and methodology in the preparation of SDs play a significant role in the biological behavior of the SDs. SDs have been prepared using a variety of pharmaceutically acceptable polymers utilizing various novel technologies. In the recent years, much attention has been paid toward the use of novel carriers and methodologies in exploring novel types of SDs to enhance therapeutic efficacy and bioavailability. The use of novel carriers and methodologies would be very beneficial for formulation scientists to develop some SDs-based formulations for their commercial use and clinical applications. In the present review, current literature of novel methodologies for SD preparation to enhance the dissolution rate, solubility, therapeutic efficacy, and bioavailability of poorly water-soluble drugs has been summarized and analyzed. Further, the current status of SDs, patent status, and future prospects have also been discussed.

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Section: Patents On Sdmentioning

confidence: 99%

RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents

et al. 2020

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“…In this study, we demonstrated the antileukemic effects of NOB at concentrations 10−100 µM in K562 cells, which were used in several anticancer studies in vitro, though it was higher than what can be achieved in vivo. Thus to increase the bioavailability and potent bioactivity of NOB in vivo, novel chemical modification, formulation or delivery system is needed to increase its solubility and reach the concentration we found in this study [45,46].…”

Section: Discussionmentioning

confidence: 85%

Nobiletin Promotes Megakaryocytic Differentiation through the MAPK/ERK-Dependent EGR1 Expression and Exerts Anti-Leukemic Effects in Human Chronic Myeloid Leukemia (CML) K562 Cells

Yen

Lin

Chuang

et al. 2020

Cells

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Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer activity. In this study, we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia (CML) K562 cells. NOB (100 μM) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3% and 46.2 ± 9.9%, respectively. NOB (10–100 μM) significantly inhibited cell growth in K562 cells. Flow cytometry analysis and immunoblotting data showed that NOB (40 and 80 μM) could modulate the cell cycle regulators including p21, p27, and cyclin D2, and induce G1 phase arrest. NOB also increased the messenger RNA (mRNA) and protein expression of megakaryocytic differentiation markers, such as CD61, CD41, and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells. These results suggested that NOB facilitated K562 cells toward megakaryocytic differentiation. Furthermore, microarray analysis showed that expression of EGR1, a gene associated with promotion of megakaryocytic differentiation, was markedly elevated in NOB-treated K562 cells. The knockdown of EGR1 expression by small interference RNA (siRNA) could significantly attenuate NOB-mediated cell differentiation. We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells. These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells. In addition, NOB when combined with imatinib could synergistically reduce the viability of K562 cells. Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy.

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“…The six isomers of MDNob in rat plasma were quantified in free form using the method employed to determine recovery. 20 Briefly, acetonitrile (50 μL) was added to the collected plasma (50 μL) in a 1.5 mL tube. The resultant mixture was vortexed for 10 s, sonicated for 10 min, and centrifuged at 3000 g for 10 min at 4 °C.…”

Section: Calculating Limit Of Detection (Lod) and Limit Of Quantifica...mentioning

confidence: 99%

“…As in the case of plasma, the accumulated free Nob was quantified using a previously developed method. 20 A portion of the collected tissue (50 mg) was transferred to a 1.5 mL tube and treated with acetonitrile (1 mL). The mixture was homogenized using an NS-310E microhomogenizer (Microtec Co., Ltd., Chiba, Japan) for 1 min and centrifuged at 3000 g for 20 min at 4 °C.…”

Section: Calculating Limit Of Detection (Lod) and Limit Of Quantifica...mentioning

confidence: 99%

Monodemethylated Metabolites of Orally Administered Nobiletin: Identification and Quantitation in Rat Plasma and Tissues

Iwashita

Shioi

Sugiyama

et al. 2023

J. Agric. Food Chem.

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Although nobiletin (Nob) is a promising functional food component in view of its multifaceted physiological activity, the metabolism of this flavonoid remains underexplored. Herein, we examine the pharmacokinetics and tissue distribution of orally ingested Nob in rats, focusing on the six monodemethylnobiletin (MDNob) isomers as the main Nob metabolites. Two of these metabolites, namely, 6-MDNob and 8-MDNob, are chemically prepared for the first time, and a method for the simultaneous determination of all six MDNobs is developed. The obtained results demonstrate the production of 8-MDNob as a novel Nob metabolite and confirm the previously reported generation of 6-MDNob and 7-MDNob as oral metabolites of Nob in vivo. Finally, a quantitative relationship is established between the amount of metabolically generated MDNobs and that of administered Nob. Thus, this work paves the way for the broad applications and safe usage of Nob.

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Development of nobiletin–methyl hesperidin amorphous solid dispersion: Novel application of methyl hesperidin as an excipient for hot-melt extrusion

Cited by 15 publications

References 44 publications

RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents

RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents

Nobiletin Promotes Megakaryocytic Differentiation through the MAPK/ERK-Dependent EGR1 Expression and Exerts Anti-Leukemic Effects in Human Chronic Myeloid Leukemia (CML) K562 Cells

Monodemethylated Metabolites of Orally Administered Nobiletin: Identification and Quantitation in Rat Plasma and Tissues

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