Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics

Pollina, G. F.; Pepe, Marco; Dean, Annalisa; Marco, Valerio Di; Marton, Daniele

doi:10.1111/jvp.12022

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…To confirm the purity of the product obtained, the following analyses were carried out: elemental analysis (C, H), 1 H and 13 C NMR, atomic absorption spectroscopy (AAS), UV-visible, pXRD, and FTIR. The obtained results from the different analyses agreed with previous publications [32,33], and are given as supplementary data.…”

Section: Methodssupporting

confidence: 89%

“…3.1. GaM: analysis of FTIR spectra, a theoretical approach Attributions of the main absorption vibrational bands of gallium maltolate were provided in these studies [32,33] with ν arom CH stretching vibration at 3070 cm −1 , ν aliph CH stretching vibration at 2910 cm −1 , ν C=C stretching vibration at 1612 cm −1 , and ν C=O stretching vibration at 1572 cm −1 . However, the last two absorption bands were inversely assigned in a third publication [38].…”

Section: Resultsmentioning

confidence: 99%

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Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Dupleichs¹,

Limelette²,

Mellier³

et al. 2022

Mater. Res. Express

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Some cancers have tropism for bone: breast, prostate, lung, kidney, and thyroid cancers are the most common. Bone metastases can be treated with surgical resection and the resulting bone defects can be filled with injectable biomaterials. Among these, calcium phosphates may be the biomaterials of choice because of their ability to locally release anticancer active ingredients. Herein, we propose the synthesis of injectable calcium phosphate cement (CPC) loaded with gallium maltolate (GaM). It is an extremely promising anticancer drug with also antibiotic and anti-inflammatory properties. This synthesis was based on commercial cement whose main component was α-tri-calcium phosphate (α-TCP), and the final product obtained after hardening was calcium-deficient apatite (CDA). Two formulations were prepared, containing 3.5% and 7% by mass of GaM (CPC-3.5G and CPC-7G respectively). Powder x-ray diffraction (pXRD), Fourier transform infrared (FTIR) spectroscopy, and magic-angle spinning nuclear magnetic resonance (NMR MAS) 31P analyses showed that the direct incorporation of GaM did not modify the final cement composition. Textural properties, such as setting time, injectability, workability, and cohesiveness, were well preserved or even improved. Additionally, the mechanical strength, although slightly reduced, remained perfectly compatible with surgical use. In vitro kinetics studies of GaM-loaded CPCs showed a controlled release of GaM (49% at 60 days for CPC-3.5G and 58% at 116 days for CPC-7G) following Fick’s law. Raman imaging was used to visualize its diffusion within the cement during in vitro release experiments. Finally, the structural integrity of the gallium complex in the CPC was confirmed using NMR MAS 71Ga.

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Section: Methodssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Dupleichs¹,

Limelette²,

Mellier³

et al. 2022

Mater. Res. Express

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“…GaMal was made by a modification of a known procedure: , gallium nitrate nonahydrate (Ga(NO 3 ) 3 ·9H 2 O corresponding to 7 g gallium, 0.10 mol) was dissolved in 200 mL water; the solution was brought at 70 °C and 45 g maltol (0.36 mol) was carefully added in 5 g portions; each addition is done when the precedent was completely dissolved. A clear solution was obtained.…”

Section: Methodsmentioning

confidence: 99%

Indium/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone

et al. 2018

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In this study, we aimed to investigate in vitro whether the synthetized indium maltolate (InMal) and gallium maltolate (GaMal) could exert either a toxic effect toward breast cancer cell line MDA-MB-231 or an agonistic activity with mitoxantrone (MTX) in comparison to fibroblast cell line NIH-3T3. Both GaMal and InMal reduced viability of MDA-MB-231, and at a lesser extent of NIH3-T3, in a dose- and time-dependent mode, the outcome was more effective in comparison to MTX sole exposure. Both GaMal and InMal toxicity was reverted by iron citrate addition on NIH3-T3, not on MDA-MB-231, showing indirectly that gallium and indium’s mechanisms of action may include iron targeting. The agonistic activity against MDA-MB-231 survival was shown pretreating with 100 μM InMal for 24 h followed by medium exchange with MTX at 10 ng mL–1 or vice-versa but not with co-incubation of both compounds. In particular, InMal pretreating resulted more protective to MTX subsequent exposure.

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“…One major medical application of maltol is related to the trimaltol gallium complex (gallium maltolate), which is one of the most developed maltol metal complexes that have reached the stage of clinical trials and veterinarian use mainly for anticancer and antimicrobial activity [ 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]. The maltol gallium complex of maltol 3:1 gallium stoichiometry is neutral, similar to the trimaltol iron complex but is slightly more lipophilic, with the n-octanol/water partition coefficient of 0.40 versus 0.32 of the trimaltol iron complex.…”

Section: Potential Applications Of Maltol and Maltol Metal Complexes In Medicinementioning

confidence: 99%

“…The basic anticancer and antimicrobial targeting of maltol gallium is the delivery of gallium to cells which mimics iron and affects iron-related metabolic pathways. In this context, the antimicrobial activity of trimaltol gallium is thought to be based on the substitution of iron by gallium causing the deprivation of iron, which is essential for the rapid growth of pathogenic microbes [ 130 , 131 , 132 , 133 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]. The anticancer activity of trimaltol gallium is thought to be based on the delivery of gallium to transferrin causing reduction of cancer cell acquisition of iron and growth reduction through the slow turnover of the iron dependent enzyme ribonucleotide reductase leading to the inhibition of DNA synthesis [ 28 , 88 , 188 , 196 , 197 , 198 , 199 , 200 , 201 , 202 ].…”

Section: Potential Applications Of Maltol and Maltol Metal Complexes In Medicinementioning

confidence: 99%

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications

Kontoghiorghes¹,

Kolnagou²,

Demetriou³

et al. 2021

IJMS

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The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980–1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978–1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA). Iron deficiency anaemia is a global health problem affecting about one-third of the world’s population. Many (and different) ferrous and ferric iron complex formulations are widely available and sold worldwide over the counter for the treatment of IDA. Almost all such complexes suffer from instability in the acidic environment of the stomach and competition from other dietary molecules or drugs. Natural and synthetic lipophilic KHP chelators, including maltol, have been shown in in vitro and in vivo studies to form stable iron complexes, to transfer iron across cell membranes, and to increase iron absorption in animals. Trimaltol iron, sold as Feraccru or Accrufer, was recently approved for clinical use in IDA patients in many countries, including the USA and in EU countries, and was shown to be effective and safe, with a better therapeutic index in comparison to other iron formulations. Similar properties of increased iron absorption were also shown by lipophilic iron complexes of 8-hydroxyquinoline, tropolone, 2-hydroxy-4-methoxypyridine-1-oxide, and related analogues. The interactions of the KHP iron complexes with natural chelators, drugs, metal ions, proteins, and other molecules appear to affect the pharmacological and metabolic effects of both iron and the KHP chelators. A new era in the treatment of IDA and other possible clinical applications, such as theranostic and anticancer formulations and metal radiotracers in diagnostic medicine, are envisaged from the introduction of maltol, KHP, and similar lipophilic chelators.

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Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics

Cited by 6 publications

References 16 publications

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Indium/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications

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