Release behavior of cupric ions for TCu380A and TCu220C IUDs

Cao, Bianmei; Xi, Tingfei; Zheng, Yudong

doi:10.1088/1748-6041/3/4/044114

Cited by 18 publications

(17 citation statements)

References 19 publications

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“…The initial rapid release of cupric ion from these Yuangong Cu-IUDs was less than that of TCu380A IUD [20] , which might lead to smaller side effects related to burst release. The copper surface area of Yuangong 365 Cu- IUD was 365 mm 2 , and the real copper surface area of TCu380A IUD was 400 mm 2 [20] .…”

Section: Discussionmentioning

confidence: 92%

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

Cao

Zheng

et al. 2009

Chin. Sci. Bull.

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Citation: Cao B M, Xi T F, Zheng Y D, et al. Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220These years Yuangong copper-bearing intrauterine devices (Cu-IUDs) have been used because of less side effects in use. The corrosion of copper is essential to the success of contraception, and the release behavior of indomethacin from medicated Cu-IUD is related to its therapeutic effect. In this study, analytical methods were established to investigate the release behavior of cupric ion of three kinds of Yuangong Cu-IUDs and indomethacin of medicated Yuangong 220 Cu-IUD. Cu-IUDs were incubated in simulated uterine solution (SUS). The concentrations of cupric ion and indomethacin were analyzed by flame atomic absorption spectrometer (FAAS) for 60 days and UV/vis 3310 spectrophotometer for 60 days, respectively. The morphology of copper after corrosion was characterized by SEM. In addition, we detected cytotoxicity by MTT of L929 mouse fibroblasts cells caused by extracts of the three Yuangong Cu-IUDs. The release behavior of cupric ion for three kinds of Yuangong Cu-IUDs was biphasic, which consisted of the initial burst release and then slow and constant release. In vitro release experiment confirmed a biphasic release of indomethacin from Yuangong 220. The copper wire of Yuangong Cu-IUDs showed uneven corrosion. The RGR value of Yuangong 365 Cu-IUD was smaller than that of medicated Yuangong 220 Cu-IUD and RGR value of medicated Yuangong 220 Cu-IUD was smaller than that of Yuangong 300 Cu-IUD. The cupric ion release and indomethacin release showed biphasic. Indomethacin increased the cupric ion release rate and might diminish the adverse effects caused by burst release of cupric ion. The toxicity grade of these three Yuangong Cu-IUDs was 4. We should canvass the adverse events of Cu-IUDs based on practical experiments, and try our best to reduce the toxicity of Cu-IUDs.Yuangong Cu-IUD, indomethacin, release rate, uneven corrosion, cytotoxicity

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Section: Discussionmentioning

confidence: 92%

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

Cao

Zheng

et al. 2009

Chin. Sci. Bull.

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“…In our earlier study we reported the initial burst release of Cu in the first three days from two commercial TCuIUDs followed by a sustained release in simulated uterine and body fluids. Further, we also showed CuIUDs get corroded faster when implanted in rat uterus (in vivo) than in simulated fluids (in vitro) (Cao et al 2008). In this study, we analyzed the Cu ion concentration dependent cytotoxicity to L929 mouse fibroblasts cells and correlated with that due to the burst release extracts from two commonly used CuIUDs -TCu220C and TCu380A.…”

Section: Discussionmentioning

confidence: 95%

“…However, their total Cu surface areas were different: 265 and 400 mm 2 respectively. Furthermore, the surface of the fine Cu wire wound on TCu380A appeared to have micro-cracks, compared to a smoother surface on Cu tubes, on the tested TCuIUDs (Cao et al 2008).…”

Section: Cu Ion Extracts From the Iudsmentioning

confidence: 89%

“…On the stem of TCu380A Cu wire is wound, which apparently releases Cu at much faster rate than Cu in the form of tubes. The two cross-arms on TCu380A and whole of TCu220C have Cu tubes wound around (Cao et al 2008;Lu et al 2008). …”

Section: Cu Extraction From Tcuiudsmentioning

confidence: 99%

“…Two aspects of Cu ion toxicity need particular attention: one, the exposure of tissues in intimate contact with the device to (often lethal) Cu ion concentrations, and two, the chronic systemic exposure of rest of the body (Arancibia et al 2003;Cai et al 2005;Cao et al 2008;Grillo et al 2009;Hefnawi et al 1974). In either case, cells take up Cu ions, and when the uptake crosses a threshold limit, the cells become apoptotic and die (Araya et al 2003;Aston et al 2000;Grillo et al 2009;Hayashi et al 2006;Obata et al 1996;Prasad et al 1996;Singh et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

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118

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Sustained release of copper (Cu) ions from Cu-containing intrauterine devices (CuIUD) is quite efficient for contraception. However, the tissue surrounding the CuIUD is exposed to toxic Cu ion levels. The objective for this study was to quantify the concentration dependent cytotoxic effects of Cu ions and correlate the toxicity due to Cu ion burst release for two popular T-shaped IUDs - TCu380A and TCu220C on L929 mouse fibroblasts. Fibroblasts were cultured in 98 well tissue culture plates and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphehyltetrazolium bromide (MTT) assay was used to determine their viability and proliferation as a function of time. For cell seeding numbers ranging from 10,000 to 100,000, a maximum culture time of 48 h was identified for fibroblasts without significant reduction in cell proliferation due to contact inhibition. Thus, for Cu cytotoxicity assays, a cell seeding density of 50,000 and a maximum culture time of 48 h in 96 well plates were used. 24 h after cell seeding, culture media were replaced with Cu ion containing media solutions of different concentrations, including 24 and 72 h extracts from TCuIUDs and incubated for a further 24 h. Cell viability decreased with increasing Cu ion concentration, with 30 % and 100 % reduction for 40 μg/ml and 100 μg/ml respectively at 24 h. The cytotoxic effects were further evaluated using light microscopy, apoptosis and cell cycle analysis assays. Fibroblasts became rounded and eventually detached from TCP surface due to Cu ion toxicity. A linear increase in apoptotic cell population with increasing Cu ion concentration was observed in the tested range of 0 to 50 μg/ml. Cell cycle analysis indicated the arrest of cell division for the tested 25 to 50 μg/ml Cu ion treatments. Among the TCuIUDs, TCu220C having 265 mm(2) Cu surface area released 9.08 ± 0.16 and 26.02 ± 0.25 μg/ml, while TCu380A having 400 mm(2) released 96.7 ± 0.11 and 159.3 ± 0.15 μg/ml respectively following 24 and 72 h extractions. The effects of TCuIUD extracts on viability, morphology, apoptosis and cell cycle assay on L929 mouse fibroblasts cells, were appropriate for their respective Cu ion concentrations. Thus, a concentration of about 46 μg/ml (~29 μM) was identified as the LD50 dose for L929 mouse fibroblasts when exposed for 24 h based on our MTT cell viability assay. The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.

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Interactions of triazole terconazole with copper and zinc cations

et al. 2023

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Terconazole is one of the triazole derivatives with an antifungal effect. It is used locally to treat vaginal yeast infections. Terconazole could interact with copper cations in the vagina or uterus of women who use an intrauterine device releasing copper cations. Other triazole derivatives in complexes with copper cations differ in their properties like toxicity or mobility. Cu2+ can be reduced in the presence of triazoles, which can lead to a Fenton-like reaction and the production of free radicals. Thus, the Cu2+/Cu+ terconazole system can be potentially dangerous. Stoichiometry, fragmentation, and stability of forming complexes were studied with tandem mass spectrometry. The Cu2+/Cu+ terconazole system was measured within the pH range of 4.0–7.2, with a concentration ratio of CuCl2 and terconazole 1:5 to 20:1, with water and ethanol as solvents (1:1). The achieved results suggest that terconazole is partially oxidized in the Cu2+/terconazole system and that this oxidation depends on the pH of a solution. Apart from the oxidized and protonated terconazole, other detected ions and complexes were not significantly affected by pH. The detection of complexes containing Cu+ is alarming because this could correspond to the occurrence of a Fenton-like reaction. Graphical abstract

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Release behavior of cupric ions for TCu380A and TCu220C IUDs

Cited by 18 publications

References 19 publications

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Interactions of triazole terconazole with copper and zinc cations

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