| Hepatocarcinoma (HC), which has a high incidence rate in china, is the disease that threatens human health due to its malignance degree. To the advanced HC, which cannot be cured by operation, and the prevention and therapy to its relapse after operation, chemotherapy is still the main cure. Presently, the main medicines for HC are: 5-fluorouracik doxorubicin (ADM) and cisplatin (DPP), etc.5-fluorouracil is a classical anti-metabolite chemotherapy to cancer, which is widely used for treating malicious carcinoma and is still the main drug for curing primary HC. But the limits of its clinical use lie in its lower selectivity, toxicity and obvious adverse drug reaction, short half-life time, and resistance to long term drug use.Galactosylceramide, a new membrane that is utilized in our experiment, is made into 5-fluorouracil Galactosylceramide liposome (5-Fu-GCL). Compared with liposome enveloped by phosphatide, it has some characteristics, such as not easily oxidized, longer retention time in blood circulation and special targeted property, etc.To investigate the preparation, pharmacokinetics, hepatic-targeted property, acute toxicity, anti-cancer effect and its mechanism of 5-Fu-GCL, a series of experiments in vivo and in vitro are adopted. The main results as follows:Part one. The preparation of 5-Fu-GCL 1. Envelopment rate experimentAfter separating 5-Fu-GCL and free 5-Fu through sephadex column chromatography, the 5-Fu content that was not enveloped was detected by HPLC. Envelopment rate was calculated in corresponding to the formula. The results showed that average envelopment rates of reverse-phase evaporation method, reverse-phase evaporation and freeze-thawing method and calcium fusion and reverse-phaseevaporation method are 25.2, 41.7 and 52.5%, respectively. The average envelopment rate of the calcium fusion and reverse-phase evaporation method is the highest.2. Morphologic observation of liposome5-Fu-GCL was spherical single-layer liposome and its size was uniform when it was observed by the electron microscope. Liposome was ball-shaped, dark colored, and more in number. The particle diameter was equality made by reverse-phase evaporation and freeze-thawing method or calcium fusion and reverse-phase evaporation method.3. Measurement of liposome's particle diameter and granularity distributionThe particle diameter distribution of 5-Fu-GCL was between 0.2-0.9 in, D50 was 0.52 in, between 0.3-0.9 in, D50 is 0.61 in and between 0.4-1.0 in, D50 is 0.68 in made by reverse-phase evaporation method, reverse-phase evaporation and freeze-thawing method and calcium fusion and reverse-phase evaporation method respectively. 0.2-0.9in, D50 0.52rn;4. Stability study4.1 Centrifuge accelerating experimentThe stability parameter was calculated by the variability of 5-Fu-GCL's absorbance before and after centrifuge. The Ke of 5-Fu-GCL made by reverse-phase evaporation method, reverse-phase evaporation and freeze-thawing method and calcium fusion and reverse-phase evaporation method were 0.047, 0.033 and 0.031 respectively.4.2 Sample keeping observation experiment5-Fu-GCL suspension was preserved in refrigerator of 4C for 6 months, then calculated its envelopment rate monthly by sephadex column chromatography, and the reduction of envelopment rate in the sixth month were 44.4%, 29.4%, 27.2%, respectively.In conclusion, the best way of enveloping 5-Fu is calcium fusion and reverse-phase evaporation method, by which we can achieve high envelopment rate, particleuniformity and stabilized property.Part two. The study of pharmacokinetics, distribution and targeted property of 5-Fu-GCL1. Study of pharmacokinetics of 5-Fu-GCLCaudal vein injection of single dose of 5-Fu-GCL (20, 40, 80 mg kg-1) and free 5-Fu, then calculate corresponding pharmacokinetic parameter based on the time process of blood drug concentration. The results showed that the blood drug concentration-time curve consisted with the first-order kinetics of one-compartment model, the main phamacokinetic...
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