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

Abstract

These 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.