Impact of nanomedicine on hepatic cytochrome P450 3A4 activity: things to consider during pre-clinical and clinical studies

Jonsson-Schmunk, Kristina; Schafer, Stephen C.; Croyle, Maria A.

doi:10.1007/s40005-017-0376-y

Cited by 4 publications

(3 citation statements)

References 194 publications

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“…CYPs are super-family enzymes. CYP1A2, -2A6, -2B6, -2C8, -2C9, -2C19, -2D6, -2E1, -2J2, -3A4, and -3A5 have been reported as main CYP isoforms expressed and functional in the human liver [27,28]. To identify the CYP isoforms responsible for the formation of 6-OH JWH-019 in HLMs, we used recombinant CYPs and assessed their respective abilities to metabolize JWH-019 using a substrate concentration of 400 µM.…”

Section: Identification Of Jwh-019-oxidating Enzymesmentioning

confidence: 99%

“…Each CYP isoform is differently expressed in the human liver. While CYP3A4 has been known as the isoform that is dominantly expressed in the liver, other isoforms such as CYP2J2 are hardly expressed in hepatic tissue [27,28]. To quantitatively determine the contribution of each CYP isoform to the formation of 6-OH JWH-019 in HLMs, we employed a relative activity factor (RAF) method.…”

Section: Identification Of Jwh-019-oxidating Enzymesmentioning

confidence: 99%

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Identification of Cytochrome P450 Enzymes Responsible for Oxidative Metabolism of Synthetic Cannabinoid (1-Hexyl-1H-Indol-3-yl)-1-naphthalenyl-methanone (JWH-019)

et al. 2023

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(1-Hexyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-019) is one of the second-generation synthetic cannabinoids which as a group have been associated with severe adverse reactions in humans. Although metabolic activation can be involved in the mechanism of action, the metabolic pathway of JWH-019 has not been fully investigated. In the present study, we aimed to identify the enzymes involved in the metabolism of JWH-019. JWH-019 was incubated with human liver microsomes (HLMs) and recombinant cytochrome P450s (P450s or CYPs). An animal study was also conducted to determine the contribution of the metabolic reaction to the onset of action. Using an ultra-performance liquid chromatography system connected to a single-quadrupole mass detector, we identified 6-OH JWH-019 as the main oxidative metabolite in HLMs supplemented with NADPH. JWH-019 was extensively metabolized to 6-OH JWH-019 in HLMs with the KM and Vmax values of 31.5 µM and 432.0 pmol/min/mg. The relative activity factor method estimated that CYP1A2 is the primary contributor to the metabolic reaction in the human liver. The animal study revealed that JWH-019 had a slower onset of action compared to natural and other synthetic cannabinoids. CYP1A2 mediates the metabolic activation of JWH-019, contributing to the slower onset of its pharmacological action.

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Section: Identification Of Jwh-019-oxidating Enzymesmentioning

confidence: 99%

Section: Identification Of Jwh-019-oxidating Enzymesmentioning

confidence: 99%

Identification of Cytochrome P450 Enzymes Responsible for Oxidative Metabolism of Synthetic Cannabinoid (1-Hexyl-1H-Indol-3-yl)-1-naphthalenyl-methanone (JWH-019)

et al. 2023

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“…The combination of this polyelectrolyte block copolymer on the surface of nanoparticles could be potential to boost the drug release in the acidic environment found in the endosomes of cancer cells [15,16,[18][19][20] . Furthermore, the PEG shell could enable prolonged blood circulation and avoid the rapid elimination of nanoparticles [21,22] .…”

Section: Research Papermentioning

confidence: 99%

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Tran¹,

Nguyen²,

Chen³

et al. 2019

pharmaceutical-sciences

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Tran et al.: Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles In this investigation, a smart nanocarrier-loaded docetaxel, a microtubules disrupting agent and vorinostat, a histone deacetylase inhibitor was developed to achieve a synergistic anticancer effect. Dual drug-loaded lipid polymer hybrid nanoparticles were prepared, with easy fabrication and favourable properties including small size, narrow distribution and a high loading effi cacy. The in vitro drug release conducted in phosphatebuffered saline, pH 7.4 and acetate-buffered saline, pH 5.5 media demonstrated the sustained, pH-dependent release profi le. The nanoparticles were effectively taken up by cells, which ensured greater suppression of cell growth. The co-delivery of both drugs exhibited a synergistic effect on the induction of cancer cell apoptosis, resulting in greater inhibition of SCC-7, MCF-7, and MDA-MB-231 cancer cells by the drug-loaded carrier. These promising results may lead to clinical applications with enhanced docetaxel activity.

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Principles and applications of nanomaterial-based hyperthermia in cancer therapy

et al. 2020

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Impact of nanomedicine on hepatic cytochrome P450 3A4 activity: things to consider during pre-clinical and clinical studies

Cited by 4 publications

References 194 publications

Identification of Cytochrome P450 Enzymes Responsible for Oxidative Metabolism of Synthetic Cannabinoid (1-Hexyl-1H-Indol-3-yl)-1-naphthalenyl-methanone (JWH-019)

Identification of Cytochrome P450 Enzymes Responsible for Oxidative Metabolism of Synthetic Cannabinoid (1-Hexyl-1H-Indol-3-yl)-1-naphthalenyl-methanone (JWH-019)

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Principles and applications of nanomaterial-based hyperthermia in cancer therapy

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