| BackgroundThe World Health Organization (WHO) statistics 1,000 people each year in the world sufferred from cancer, while the number of deaths is about 60,000 accounting for 12% of global deaths. There is about 1.8 million new cancer patients each year,1.4 million dead.an average of 1.3 every 3 minute, people died of cancer. Primary liver cancer is a common malignant tumor, its incidence and mortality are high. Liver cancer incidence locates the fifth. Mortality rate ranked the third[1]. According to statistics 55% liver cancer occurred in China, while the incidence and death rates are higher. Its progress is rapid and life quality is poor,which is far less effective disease in all tumors.And most patients'diagnosis is late.Hepatic carcinoma is not sensitive to chemotherapy and radiotherapy. Also chemotherapy is poor targeting, poor efficacy, toxic side effects and other defects.The local or Combination therapy to liver cancer is a major focus. a high-frequency electromagnetic wave, the organization polar molecule (mainly water molecules, ions and charged colloidal protein) under the action of the microwave generates friction heat, leading to coagulation necrosis of tumor tissue, and liver tissue is rich of water. The features in the ultrasound-guided inserted within the tumor tissue, can quickly produce up to about 65℃-100℃temperature. However, there is often kinds of problems,such as incompleted ablation,residual tumor tissue and recurrence and so on. The microwave treatment combined with other treatment is an important local method to liver tumor treatment.Controlled-and sustained-release drugs are the third generation.The traditional drugs are embedded in the matrix or vector, using matrix adsorption, viscosity, adhesion or membrane barriers stand, improving drug stability, reducing blood concentration peak and delaying the drug release rate and improving drug targeting positioning. It solves the problems sucn as the traditional drugs, especially anticancer drugs with short half-life, difficult to maintain the plasma concentration during long, systemic toxic side effects. Most patients are suffering from tolerating such shortcomings, which is an important trends and in finding new treatments In the treatment, the study found that the use of nano-scale polymer particles as a new drug delivery and controlled release carrier, because of its small size super-micro through targeting the role of positioning and release into the body's cells, of nucleic acids, proteins, etc. material for the molecular level of life treatment, not only improved the efficacy of existing drugs, but also significantly reduced the adverse reactions of their own, the role of nano-drug targeting mechanism in accordance with its three different types:①active targeting, the antibodies or ligand-specific targeting molecules, such as coupling to the surface of particle orientation distribution of drugs to target tissue;②passive targeting., by control and modified the physical or chemical properties of the vector (size, shape, hydro-philicity, surface charge and the wall aperture, etc.) can control its distribution and drug release characteristics in the body, or to choose the nanoparticles which targeted to the body of various organizations and different disease affinity can also achieve the purpose;③physical and chemistry targeting, such as:use of local magnetic field in vitro, with super paramagnetic iron nanoparticles as a carrier at the external magnetic field under the directional distribution in a predetermined target tissue. By changing the physical and chemical properties of the nanoparticles, such as size, mass, charge and water affinity, can reduced non-specific interactions with non-targeting organs, tissues and cells, thus increasing the target position/non-target ratio of the drug.In this study, chitosan is as a carrier, packaging epirubicin to prepare the drug into chitosan microspheres. Chitosan microspheres is a more practical forms of drug delivery. Chitosan microspheres means of drug dissolved or dispersed in the carrier in the form of small spherical solid particle whose size ranges from 1 to 250μm.Chitosan (CS) is a polycationic polysaccharide derivatives which is widely exist in nature, also known as soluble chitin, chitosan, etc. from D-glucosamine and N-acetyl-D-glucosamine composition, based onβ-(1,4)glycosidic bond linking the straight-chain polysaccharide, the chemical known as (1,4)-2-amino-2-deoxy-β-D-glucose, its structure similar to cellulose, chitosan is non-toxic, has good biocompatibility and degradability. Chitosan microspheres can selectively gathered to the tumor cells and play its anti-tumor effects.Doxorubicin is the anthracycline antitumor antibiotics, because of its broad spectrum anti-tumor drug whose main side effects is its cardiac toxicity. It Can lead to severe myocardial injury and heart failure, and the extent of damage is closely related to dose.to The main method of reducing their cardiac toxicity is the application of drug delivery,biodistribution changes to reduce the distribution in heart tissue, increasing local dose in tumor.This study use CS as a raw material used in this study.Using W/O type emulsion-Curing Preparation epirubicin-chitosan microspheres to detect physical and chemical properties of microspheres,by a simple injection to treat tumors in mice liver tumor. It was observed by treating tumor proliferation. After that, we do next experiment. It is combined with microwave ablation to explore the combined effect in treating liver tumor, and to find a new combination therapy against liver cancer.Objective:1.Explore the drug-loaded chitosan microspheres as anti-cancer drugs combined with microwave treatment of hepatic tumor is feasible.2.Preparation of the load model drug epirubicin (EPI) of the chitosan microspheres (CS) and to detect drug-loaded microspheres and in vitro release properties of the particle size. 3.Pairs of mice in vivo tumor inhibition test to prove that the load epirubicin-chitosan microspheres as compared with ordinary anti-cancer drugs have a better anti-tumor effect in vivo, is more suitable as a carrier of chemotherapeutic drugs.4.Chitosan microspheres combined with microwave treatment of transplanted tumors in mice to prove that microwave therapy alone compared with other method the tumor inhibition rate compared to higher.Methods:1.Epirubicin-loaded chitosan microspheres were prepared by using emulsion-chemical cross linking technique.2.The surface morphology and particles size of chitosan microspheres were observed by scanning electron microscope. Ultraviolet spectrophotometer was used to analyze the entrapment efficiency, entrapment efficiency and cumulative release rates of epirubicin-loaded chitosan microspheres.3.Totally 24 mice with transplanted subcutaneous H22 HCC were divided into 4 groups, which were respectively treated by microwave coagulation therapy, intratumoral injected with physiological saline after microwave microwave coagulation therapy, intratumoral injected with epirubicin after microwave coagulation therapy, intratumoral injected with CS-EPI after microwave coagulation therapy.The tumor inhibitory rate was calculated.Results:1.The microspheres'size distribution was Uniform. The average diameter was 105um, The ratio of drug loading was 11% and the entrapment was 80%. The drug cumulative release rate in vitro after 2weeks was 84%.2.Chitosan microspheres is an effective epirubicin local sustained release formulation, has good anti-tumor effect.3.Compared with the pure microwave group, the tumour-inhibition rate of other groups were 11%,20%,47%.Conclusion:4.1. W/O type emulsion-Preparation of curing Epirubicin-chitosan microspheres shape the rules of uniform particle size distribution with high encapsulation efficiency and good release properties.2. With chemotherapy alone compared with drug-loaded chitosan microspheres on tumor in vivo anti-tumor effect in mice strong, chitosan microspheres is more suitable as a carrier of new chemotherapy drugs.3. Microwave combined with local intratumoral injection drug containing chitosan microspheres of treatmenting mice reduces tumor volume, gets a higher inhibition rate; microwave and intratumoral injection of drug delivery microspheres of this treatment model is worthy of further study.There may be an effective treatment method for advanced liver cancer.
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