Fabrication And Properties Of Fe₃O₄/Chitosan Thermosensitive Gel Composite

Some problems exist in the course of curing bladder cancer, such as poor drug effect, repeated injection, et al. So the patients seriously suffer from the cancer and the high curing fee. If drug can be targeted delivered to the bladder wall and sustained release, the questions talked above could be solved in some degree. Besides pharmacotherapy, if hyperthermia can be introduced into curing course, there will be a new effective way for bladder cancer therapy.In this paper, Fe₃O₄/chitosan thermosensitive gel composite were prepared and characterized, which had the magnetic property and sustained release property. In the applied magnetic field, the composite particles could move to bladder wall. And besides, hyperthermia could be carried out taking the advantages of microwave absorption of Fe₃O₄. Some influencing factors were studied systemetically, and the preparation processes were optimized. The main content and results are as follows.Fe₃O₄ nanoparticles were prepared by the method of coprecipatation, which were aged by waterbath heat-treatment, microwave irridation and hydrothermal treatment, respectively and charactrized by X-ray powder diffraction analysis (XRD), Transmission Electron Microscope (TEM), Vector Network Analyzer and Vibrating Sample Magnetometer (VSM) etal. The results indicated that the crystallinity of Fe₃O₄ got improved after aged and the mean size of the particles was less than 25nm. The particles aged by hydrothermal treatment had higher specific saturation magnetization (M_s) and crystallinity and the Ms could reach to 80.0emu/g after hydrothermal treatment for 4h. With the absorber thickness of 7mm, the reflection loss could reach to -13dB at the frequency of 2450MHz, which demonstrated that Fe₃O₄ had microwave absorption. Fe₃O₄ nanoparticles irradiated for 20min had lower M_s, coercivity (H_c) and remanent magnetization (M_r). It could be found that Fe₃O₄ nanoparticles had good supermagnetic property when prepared by the means of coprecipitation connected with low power microwave irradiation.The parameters of preparing chitosan/β-glycerophosphate thermosensitive gel were optimized. The final sol could be gelation within the controlled time in the 37℃waterbath.Fe₃O₄ nanoparticles were added into chitosan gel. And the composite particles were obtained by grinding Fe₃O₄/chitosan gel which was completely dried under vacuum at 37℃. XRD and IR results indicated that there was no chemical reaction between Fe₃O₄ and gel carrier. SEM results showed that due to high viscosity and drainage action of gel, the Fe₃O₄ nanoparticles aggregated seriously. According to the magnetic hysteresis loop, the magnetic property of composite particles decreased sharply, but the composite as-prepared still had magnetic response property. The simulation experiment in vitro showed that the composite particles were well targeted to the wall in the applied magnetic field. Drug sustained-release property of composite particles was also studied, using ciprofloxacin hydrochloride as model. From the results, we could see drug release mainly depended on the diffusion of drug and besides, particles with smaller diameter and higher drug content had higher drug release rate. Take the particles whose drug content was 10% and the size was 30-60 mesh for example, 65% drug was released within 12h, but when release time was 72h the release rate was 80%. So it illustrated that composite as-prepared had good drug sustained-release property. The results were well matched with Higuchi model.Cytotoxicity evaluation using L-929 cells as model system showed that the morphology of cells was normal and the composite were nontoxic. MTT analysis confirmed that there were no signicant difference between the experiment group and control group in cell avtivity, the toxicity level were 0 level. Human hepatoma SMMC-7721 xenograft model in nude mice were build and Fe₃O₄/chitosan gel were injected into the tumours. The thermal effect of material was preliminary studied. We could see from the results that the tumours became small gradually while it did no harm to the organ closed to tumour. So it was an effective way to cure tumour.