Study on pharmacokinetics and tissue distribution of single dose oral tryptanthrin in Kunming mice by validated reversed-phase high-performance liquid chromatography with ultraviolet detection

Zhang, Xiaoyan; Xia, Jie; Zhang, Wenjing; Luo, Yao; Sun, Wenbo; Zhou, Weili

doi:10.1016/j.imr.2017.05.001

Cited by 20 publications

(5 citation statements)

References 19 publications

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“…[20][21][22][23] Even in animal models, multiple biopsies of tumors are technically challenging, and so researchers typically carry out PK studies by collecting samples from multiple animals sacrificed at different time-points, producing averaged population data that do not accurately capture intra-tumor variability from individual animals. 24 Furthermore, these experiments are being performed ex vivo, and may not accurately capture the physiological behavior of a tumor within its in vivo milieu. More generally, such analyses are challenging to perform for a variety of reasons-for instance, the probe needs to withstand insertion into solid tissue with minimal sensor damage, and must be sufficiently resistant to biofouling to enable robust measurement over extended periods of time.…”

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals

Seo

Correa

et al. 2021

Preprint

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The efficacy and safety of a chemotherapy regimen fundamentally depends on its pharmacokinetics. This is currently measured based on blood samples, but the abnormal vasculature and physiological heterogeneity of the tumor microenvironment can produce radically different drug pharmacokinetics relative to the systemic circulation. We have developed an implantable microelectrode array sensor that can collect such tissue-based pharmacokinetic data by simultaneously measuring intratumoral pharmacokinetics from multiple sites. We employ gold nanoporous microelectrodes that maintain robust sensor performance even after repeated tissue implantation and extended exposure to the tumor microenvironment. We demonstrate continuous in vivo monitoring of concentrations of the chemotherapy drug doxorubicin at multiple tumor sites in a rodent model, and demonstrate clear differences in pharmacokinetics relative to the circulation that could meaningfully affect drug efficacy and safety. This platform could prove valuable for preclinical in vivo characterization of cancer therapeutics, and may offer a foundation for future clinical applications.

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Section: Introductionmentioning

confidence: 99%

Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals

Seo

Correa

et al. 2021

Preprint

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“…Eighty Kunming mice40 were randomly divided into three groups: 30 mice in the control group, 45 mice in the experimental group, and 5 mice in the blank group. All of the mice were fasted for 12 hrs before experiments, with free access to water.…”

Section: Characterizationmentioning

confidence: 99%

<p>Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery</p>

Liu

Zhu

Bao³

et al. 2019

IJN

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Background Like most protein macromolecular drugs, the half-life of rhIFNɑ-2b is short, with a low drug utilization rate, and the preparation and release conditions significantly affect its stability. Methods A nanoporous ion-responsive targeted drug delivery system (PIRTDDS) was designed to improve drug availability of rhIFNα-2b and target it to the lung passively with sustained release. Chitosan rhIFNα-2b carboxymethyl nanoporous microspheres (CS-rhIFNα-2b-CCPM) were prepared by the column method. Here, an electrostatic self-assembly technique was undertaken to improve and sustain rhIFNα-2b release rate. Results The size distribution of the microspheres was 5~15 μm, and the microspheres contained nanopores 300~400 nm in diameter. The in vitro release results showed that rhIFNα-2b and CCPM were mainly bound by ionic bonds. After self-assembling, the release mechanism was transformed into being membrane diffusion. The accumulative release amount for 24 hrs was 83.89%. Results from circular dichrogram and SDS-PAGE electrophoresis showed that there was no significant change in the secondary structure and purity of rhIFNα-2b. Results from inhibition rate experiments for A549 cell proliferation showed that the antitumor activity of CS-rhIFNα-2b-CCPM for 24 hrs retained 91.98% of the stock solution, which proved that the drug-loaded nanoporous microspheres maintained good drug activity. In vivo pharmacokinetic experimental results showed that the drugs in CS-rhIFNα-2b-CCPM can still be detected in vivo after 24 hrs, equivalent to the stock solution at 6 hrs, which indicated that CS-rhIFNα-2b-CCPM had a certain sustained-release effect in vivo. The results of in vivo tissue distribution showed that CS-rhIFNα-2b-CCPM was mainly concentrated in the lungs of mice (1.85 times the stock solution). The pharmacodynamics results showed that CS-rhIFNα-2b-CCPM had an obvious antitumor effect, and the tumor inhibition efficiency was 29.2%. Conclusion The results suggested a novel sustained-release formulation with higher drug availability and better lung targeting from CS-rhIFNα-2b-CCPM compared to the reference (the stock solution of rhIFNα-2b), and, thus, should be further studied.

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“… 46 , 47 In contrast, a number of metabolites such as tryptanthrin play a renoprotective role. 48 Notably, tryptophan can be transformed into two beneficial metabolites by TPH, and our recent studies indicated the two metabolites, 5-MTP and melatonin, exhibited a renoprotective role in CKD. 10 , 11 , 16 Both TPH-1 and TPH-2 convert tryptophan to 5-hydroxytryptophan (5-HTP).…”

Section: Discussionmentioning

confidence: 99%

Poricoic acid A as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription

Chen

et al. 2020

Therapeutic Advances in Chronic Disease

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Background: Renal fibrosis is the common feature of chronic kidney disease (CKD). However, few drugs specifically target fibrogenesis due to the lack of an effective therapeutic target. Hence, it is urgent to find a therapeutic strategy that inhibits renal fibrosis. Here, we identified that poricoic acid A (PAA) as the modulator of tryptophan hydroxylase-1 (TPH-1), the key enzyme in tryptophan metabolism, exerted potent anti-fibrotic effects in the kidney. Methods: Lentiviral vector, luciferase reporter activity assay and co-immunoprecipitation were used. The animal model of unilateral ureteral obstruction and adenine-induced chronic renal failure as well as transforming growth factor (TGF)-β1-treated epithelial cells NRK-52E and fibroblasts NRK-49F were used. Results: TPH-1 was gradually decreased during CKD progression, while PAA treatment significantly increased TPH-1 expression to suppress renal fibrosis. Pharmacological overexpression of TPH-1 by PAA treatment exhibited anti-fibrosis and was linked to Wnt/β-catenin signaling activity. TPH-1 exhibited anti-fibrotic effects by suppressing epithelial cell injury and fibroblast activation, and PAA promoted TPH-1 expression and then suppressed the Wnt/β-catenin signaling pathway via regulating the protein stability of β-catenin and β-catenin-mediated transcription. TPH-1 overexpression enhanced the anti-fibrotic effects of PAA, while TPH-1 deficiency weakened the anti-fibrotic effects of PAA, indicating that TPH-1 was required for the anti-fibrotic effects of PAA. Conclusion: PAA as a modulator of TPH-1 expression attenuated renal fibrosis through regulating the Wnt/β-catenin signaling pathway by acting on the protein stability of β-catenin and β-catenin-mediated transcription. TPH-1 was required for PAA to exert anti-fibrosis.

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Study on pharmacokinetics and tissue distribution of single dose oral tryptanthrin in Kunming mice by validated reversed-phase high-performance liquid chromatography with ultraviolet detection

Abstract: Graphical abstract

Cited by 20 publications

References 19 publications

Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals

Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals

<p>Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery</p>

Poricoic acid A as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription

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