| Chitosan is the only biodegradable natural polymer with great potential for pharmaceutical applications due to its degradability and biocompatibility. Previous studies revealed that the consumption of CTS had a beneficial lowering effect on plasma lipids both in animals and humans. However, while CTS was believed to be of low toxicity and safe in the diet, some reports have suggested that the side effects in most trials included constipation, nausea, bloating, indigestion, and abdominal pain after excessive intake of CTS. And the pharmaceutical industry always attempts to design drugs as microspheres to control the release and elevates the bioavailability.CTS-MP and WSC-MP were prepared by the spray-drying technique. The yields as the main evaluation index, the conditions of the preparation of microspheres were investigated in concentration of chitosan and water-soluble chitosan, inlet temperature, flow rate and hot air flow. The preparation condition for both products was optimized via single factor experiment. The product was characterized in physicochemical properties, particles size and surface morphology etc. As a result, scanning electron microscopy (SEM) micrograph showed that the microspheres were nearly spherical in shape; the mean size of CTS microspheres was 4.07μm varied from 1.50-7.21μm and the WSC microspheres was 2.00μm varied from 0.85-3.58μm, respectively.The LD50 of CTS, WSC, CTS-MP and WSC-MP was determined by Horn method. The results showed the LD50 of WSC-MP was 4080mg/kg. By contrast, CTS, WSC and CTS-MP failed to detect the median lethal dose. The results of MTD experiment showed that the MTD of CTS and CTS-MP by oral administration was greater than 10000mg/kg. It indicated that the CTS and CTS-MP were the actual non-toxic substances. Consequently, CTS and CTS-MP were safe medicinal for human.Hypolipidemic effect of CTS-MP and WSC-MP was studied in vitro and in vivo. The effects of CTS-MP and WSC-MP on binding capacities of lipids and bile salts was investigated in the conditions simulating human gastrointestinal tract in vitro. The results indicated that the binding capacities of lipids and bile salt of CTS-MP and WSC-MP were more effective than the common CTS and WSC. Rats were fed with high-fat diets for 2 weeks to establish the hyperlipidemic condition and treated with CTS-MP, WSC-MP, CTS and WSC for 4 weeks. Results showed that CTS microspheres and WSC microspheres reduced TC, TG, LDL-C and plasma viscosity significantly, and increased the serum superoxide dismutate (SOD) levels significantly.The weight reduction effect of CTS-MP and WSC-MP on obese rats was taken for 4 weeks. As a results, CTS-MP and WSC-MP can significantly lower the body weight, lighter the weight of fat tissues of the high fat diet rats and do not curb appetite. CTS-MP and WSC-MP can also significantly decrease the level of total cholesterol(TC) ,triglyceride(TG)and low density lipoprotein(LDL)in the serum of the high fat diet rats.In order to develop a more effective medicine for lowering lipids or body weight, CTS-MP, which has the effect on lowering lipids and body weight, was used to envelop the CAP that have the same effect as CTS-MP to achieve the cooperation. The conditions of the preparation of CTS-CAP-MP were investigated by the orthogonal and single factor experiments; the evaluation index included the entrapment efficiency and the drug loading efficiency. The yields and particles size as the main evaluation index, the conditions of the preparation of microspheres were investigated in inlet temperature, flow rate and hot air flow. The preparation condition for both products was optimized via single factor experiment. Results showed that the CTS-CAP-MP have a spherical shape, the particle size was 4.50μm, the Zate was +3.48mV; the drug entrapment efficiency was can reach to 85.17%±0.78; the drug loading efficiency was 8.87%±0.08.
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