The Release Characteristics And Biocompatibility Of The Modified Cu/LDPE Nanocomposites

The copper-bearing intrauterine device (Cu-IUD) is the most popularly used IUD at present. However, after Cu-IUDs insertion, some side effects such as pelvic inflammatory disease, pain and bleeding have been observed by some researchers. Concerns about side effects remain stubborn obstacles to a wider use of modern IUDs. In order to decrease the side effects of Cu-IUD, Cu/LDPE nanocomposites were prepared for IUD in our previous study. Further, zinc, zinc oxide and indomethacine were added into Cu/LDPE nanocomposites in this study to decrease the side effects more effectively.Zinc ion has the function of contraceptive action, antibacterial effects, wound healing and tissue repair of the endometrium. Compared with zinc and zinc oxide bulk, zinc and zinc oxide nanoparticles shew much stronger antibacterial properties. Furthermore, the anticoagulant properties of zinc oxide nanoparticles are excellent. It indicates that nanoparticles of zinc and zinc oxide could decrease the side effects of IUD more effectively. At the same time, indomethacine (IDM) can alleviate menorrhagia that is responsible for the extraction of Cu-IUD. Therefore, by using low-density polyethylene as the carrier , composites of Cu/Zn/LDPE,Cu/ZnO/LDPE and Cu/IDM/LDPE were prepared by method of compressing molding. And the properties of the composites were deeply investigated.Investigation on Zn²⁺ transformation ratios of zinc and zinc oxide in the simulated uterine solution shows that the Zn²⁺ transformation ratios are affected by human serum albumin in the simulated uterine solution. By the binding of zinc ions with human serum albumin, the dissolutions of zinc and zinc oxide and the transformation ratio of Zn²⁺ can be obviously accelerated in initial stages. But after denaturalization of human serum albumin in later time, Zn²⁺ transformation ratio becomes lower.It has been found that the release rates of Cu²⁺ and Zn²⁺ of Cu/Zn/LDPE and Cu/ZnO/LDPE nanocomposites can keep stable during the experimentation time after a burst release at beginning. So IUD prepared with this composite should not only have high contraceptive effect but also reduce the side effects like infection, pain and bleeding. With the variation of one kind of nanoparticle content, the ion rate of the other kind of nanoparticles decreases or unchange. The reason is that the copper and zinc nanoparticles (or zinc oxide nanoparticles) can inhibited the dissolution mutually and at the same time provide the pathways for iron release to each other. So the proper release rate of Cu²⁺ and Zn²⁺ in the nanocomposites can be achieved by adjusting the relative contents of copper and zinc.Shake flask test was employed to evaluate the antibacterial activity of the composites with 35wt% copper particles and 15wt% zinc or zinc oxide particles. The results show that the antibacterial activity of these composites, in descending order of strength, is as follows: Cu/ZnO/LDPE composite, Cu/LDPE composite and Cu/Zn/LDPE composite. The antibacterial activity of all the composites becomes worse if they are immersed in the simulated uterine solution for a month. Furthermore, the antibacterial activity of the nanocomposites is better than that of the microcomposites. Among all the composites, only Cu/ZnO/LDPE and Cu/LDPE nanocomposites, especially the latter, can keep good antibacterial activity even for a month.The blood compatibility of the nanocomposites with 15% nanoparticles was evaluated in terms of the plasma recalcification time,the hemolysis rate and platelets adhesion. Among ZnO/LDPE,Zn/LDPE and Cu/LDPE nanocomposites, ZnO/LDPE nanocomposite has the lowest hemolysis rate and the longest plasma recalcification time. The results show that a small amount of platelets on the surface of ZnO/LDPE are detected. However, a lot of activated platelets on the surface of Zn/LDPE aggregate and spread out, which may trigger the formation of thrombus. Consequently, compared with zinc nanoparticles, zinc oxide nanoparticles show good antibacterial effect and blood compatibility. The above results indicated that zinc oxide nanoparticles are more suitable for the material of IUD with low side effects. Cu²⁺ release and IDM release from Cu/IDM/LDPE nanocomposites were studied. IDM in the composites diffuses out through pore channels. Some of the pores created by the dissolution of copper nanoparticles provide diffusion path for IDM release and enhance the release rate of IDM. The preparation process of the nanocomposite was improved in this study by distributing IDM in the surface layer of the nanocomposite. This nanocomposite exhibits much higher release rate of IDM after incubation for 3 months and lower initial burst of Cu²⁺ than the matrix-type nanocomposite, implying that it can enhance the availability ratio of IDM, prolong the service life of IDM, and reduce the burst effect of Cu²⁺.