Acidic dissociation constants of folic acid, dihydrofolic acid, and methotrexate.

Poe, Martin

doi:10.1016/s0021-9258(17)40312-7

Cited by 152 publications

(71 citation statements)

References 20 publications

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“…This self-sensitized degradation mechanism probably explains why we observed higher degradation rate (and thus quantum yield) at pH 7 than at pH 3. This assumption is furthermore supported by the protonation site located on the diamino-pteridine and corresponding to the dissociation constant (pK a ) of 5.71 (Poe, 1977;Rubino, 2001).…”

Section: Resultsmentioning

confidence: 85%

Photodegradation of methotrexate in aqueous solution: degradation kinetics and identification of transformation products

Espinosa

Nélieu

Lieben

et al. 2021

Environ Sci Pollut Res

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Methotrexate is an antineoplastic folate analog of high environmental concern, due to its low biodegradability and toxicological properties. This study focused on its photodegradation under two irradiation conditions, aiming to be representative of environment (300-450 nm) and drinking water treatment (254 nm). The photodegradation experiments were conducted at two pH, to vary the methotrexate ionization state and to produce a large variety of transformation products (TPs). The degradation kinetics determined through LC-UV monitoring were contrasted according to pH and irradiation wavelength. However, the quantum yields were independent of ionization state at 254 nm and the changes in kinetics at higher wavelengths were attributed to a change in the degradation mechanism. The TPs formed during the reactions were identi ed by UHPLC-MS/MS, using both the positive and negative modes. Among the eleven proposed structures, ve were described as methotrexate TPs for the rst time. The TPs result from N-demethylation, glutamic acid oxidation and C-N cleavage, all of them leading to further degraded photoproducts presenting modi ed or lost glutamic acid part. This was made possible thanks to the negative mode, which allowed the exploration of the glutamic acid moiety modi cations. Cytotoxicity assessment on A549 cancer cells demonstrated that all photoproducts formed at pH 7 were less toxic than the parent compound.

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Section: Resultsmentioning

confidence: 85%

Photodegradation of methotrexate in aqueous solution: degradation kinetics and identification of transformation products

Espinosa

Nélieu

Lieben

et al. 2021

Environ Sci Pollut Res

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“…Fourth, whether or not the same transfer rate constant exists in normal tissues compared with the tumor tissues is questionable. Nevertheless, the difference in pH between the tumor and normal tissues is still considerable (42,43). This difference in pH and resultant changes in transporter properties (44) may promote an asymmetrical transport of MTX into the tumor compared with normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Microdialysis-directed Intra-tumor Pharmacokinetic Modeling of Methotrexate in Mice and Humans

2016

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Purpose. To develop a quantitative pharmacokinetic model to characterize the disposition of methotrexate (MTX) at tumor site in tumor-bearing mice and to predict MTX concentrations in the human tumor. Methods. The plasma profiles of MTX were obtained from normal mice, while microdialysis technique was employed to characterize the time course of MTX in tumor from breast tumor-bearing mice. Disposition profiles of plasma and tumor were analyzed by a hybrid physiologically-based pharmacokinetic (hPBPK) model that incorporates physiologically-relevant parameters such as tumor blood flow and volume, while plasma concentrations were used as a forcing input into the vascular-interstitial spaces of the tumor. The plasma profiles were initially described by a biexponential decay model to obtain a forcing function that enters into the vascular-interstitial spaces in the tumor. Using a defined forcing function, the tumor free concentrations were fitted to the hPBPK model. Based on the model developed, sensitivity analysis was conducted with a perturbation of PK parameters to predict different scenarios of intratumoral MTX transport. The relevant physiological PK parameters from the mouse model were then scaled-up and utilized to simulate human tumor concentrations. Results. The mouse hPBPK model adequately characterized the concentration-time profiles of MTX in both plasma and tumor and produced various transfer rate constants between plasma and tumor. Our model was also able to reasonably predict MTX concentrations in the human tumor when human physiological data were utilized. Conclusions. The hPBPK model was able to quantitatively characterize the atypical transport of MTX in the tumor, supporting the idea that microdialysis is a valuable tool to study tumor biodistribution of drugs and to predict tumor concentrations in humans based on the pre-clinical data. This information can ultimately aid in the development of anticancer drugs with improved PK profiles. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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“…The average particle diameter was 80.5 ± 0.9, with the peak located in the range of 90-100 nm (Figure 2A). The zeta potential of the MNP aqueous solution was −50.4 ± 1.3 mV, indicating high colloidal stability of the solution (Figure 2B) [66]. The polydispersity index was 0.20 ± 0.01, which indicates the homogeneity of the suspension under study [67].…”

Section: Characterization Of Magnetic Iron Oxide Nanoparticlesmentioning

confidence: 91%

DNA/Magnetic Nanoparticles Composite to Attenuate Glass Surface Nanotopography for Enhanced Mesenchymal Stem Cell Differentiation

Ishmukhametov¹,

Batasheva²,

Rozhina³

et al. 2022

Polymers

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Mesenchymal stem cells (MSCs) have extensive pluripotent potential to differentiate into various cell types, and thus they are an important tool for regenerative medicine and biomedical research. In this work, the differentiation of hTERT-transduced adipose-derived MSCs (hMSCs) into chondrocytes, adipocytes and osteoblasts on substrates with nanotopography generated by magnetic iron oxide nanoparticles (MNPs) and DNA was investigated. Citrate-stabilized MNPs were synthesized by the chemical co-precipitation method and sized around 10 nm according to microscopy studies. It was shown that MNPs@DNA coatings induced chondrogenesis and osteogenesis in hTERT-transduced MSCs. The cells had normal morphology and distribution of actin filaments. An increase in the concentration of magnetic nanoparticles resulted in a higher surface roughness and reduced the adhesion of cells to the substrate. A glass substrate modified with magnetic nanoparticles and DNA induced active chondrogenesis of hTERT-transduced MSC in a twice-diluted differentiation-inducing growth medium, suggesting the possible use of nanostructured MNPs@DNA coatings to obtain differentiated cells at a reduced level of growth factors.

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Acidic dissociation constants of folic acid, dihydrofolic acid, and methotrexate.

Cited by 152 publications

References 20 publications

Photodegradation of methotrexate in aqueous solution: degradation kinetics and identification of transformation products

Photodegradation of methotrexate in aqueous solution: degradation kinetics and identification of transformation products

Microdialysis-directed Intra-tumor Pharmacokinetic Modeling of Methotrexate in Mice and Humans

DNA/Magnetic Nanoparticles Composite to Attenuate Glass Surface Nanotopography for Enhanced Mesenchymal Stem Cell Differentiation

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