Study On Surface Modification Of Copper/low-density Polyenthylene Composite For Intrauterine Device

Copper-containing intrauterine device (Cu-IUD) is a cheap, convenient, reliable and reversible contraceptive device that has been used worldwide. However, some undesirable side effects, such as bleeding, pain and inflammatory disease, have not been overcome yet in clinical use. To reduce the side effects which occurred after the insertion of Cu-IUD, a novel copper/low-density polyethylene composite and its device (Cu/LDPE composite IUD) has been developed in our previous works. More studies had shown that this novel Cu/LDPE composite IUD not only has an excellent contraceptive effect, but also can eliminate these various side effects (such as the initial cupric ion burst release, bleeding, etc.) remarkably.For further enhancing the biocompatibility of Cu/LDPE composite IUD and give them new biological functions, this work used the surface modification technique to achieve this purpose, which is mainly due to the surface modification will keep the natural properties of the matrix materials unchanged, and can also graft some new biomaterials onto the surface of the matrix, which giving the matrix new biological functions. Cu/LDPE composite IUD as an implanted medical device need good biocompatibility, and it should be much safer, more effective, and has more biological functions. So enhancing its biocompatibility and giving more biological functions to Cu/LDPE composite IUD is a very meaningful work.This work includes four main parts. The first part is activating the surface of the Cu/LDPE composite by using UV-grafting method. To prepare for the electrostatic self-assembly, the poly(acrylic acid) was grafted on the surface of the Cu/LDPE composite to make its surface with a negative charge. After UV-grafting treatment, the chitosan was coated on the surface of composite for proving the electrostatic self-assembly method is feasible. Finally, the cupric ion release behavior of these samples in vitro has been studied. The results show that the pretreatment process and UV irradiation did not influence the cupric ion release behavior of the Cu/LDPE composite. However, the composite has grafted with poly(acrylic acid) and chitosan would be more stable. The second part of this work is that a multilayer film containing indomethacin (IDM), which made up of chitosan (CHI) and alginate (Alg), has been grafted onto the surface of the Cu/LDPE composite. The cupric ion and IDM release behaviors in vitro have been studied in this work. It can be found that this drug delivery multilayer film can reduce the initial release rate of cupric ion and keep the release rate of cupric ion at a stabilizing range. In addition, while releasing cupric ion in vitro, the IDM drugs can also be susutained released. And its release duration can be controlled by tailoring the multilayer films.The third part of this work is to graft the sulfonated chitosan onto the surface of the Cu/LDPE composite. Since more studies have shown that sulfonated chitosan has many excellent biological functions, such as anti-coagulation, antibacterial,, self-cleaning effect and so on. Grafted the sulfonated chitosan onto the surface of Cu/LDPE composite will enhance anti-coagulation, and will allow the composite to have antibacterial and anti-inflammatory properties. Therefore, this work has prepared sulfonated chitosan and grafted them on the Cu/LDPE surface. The cupric ion release behavior of these composite grafted with sulfonated chitosan has been studied in vitro, too. In addition, sulfonated chitosan containing IDM film has been prepared and grafted onto the surface of Cu/LDPE, and the release behaviors of IDM and cupric ion have been studied in vitro.The fourth part is mainly to tailor the structure of this drug delivery multilayer film to control the IDM and cupric ion release rates. It could found that preparing the drug-loading chitosan film with high concentration (3w/v.%) of chitosan solution and cross-linking the chitosan film would reduce the initial release rate of IDM. The drug delivery multilayer film prepared with chitosan/alginate or chitosan/poly(acrylic acid) will influence the initial release rate of IDM.It hopes that these research works above could provide some new ideas and methods to the Cu/LDPE composite IUD development.