| Hepatocarcinoma which is a malignant tumour has seriously affected the human health because of the high incidence and the high mortality rate. According to statistics, in our country the hepatocarcinoma cases take55%of the global cases and the death toll from hepatocarcinoma is about45%of the total number of people die from hepatocarcinoma all over the world. So the treatment of hepatocarcinoma becomes a fiendish problem that is in dire need to be overcome. Andrographolide with the abilities of clearing heat, expelling miasma, cooling blood and detumescence, which belongs to a diterpenoid Lactone composition, is one major active ingredient extracted from Andrographipaniculata(Burm. f.)Nees. In the recent research, andrographolide has been found to posses multi-pharmacological effect including anti-tumor and immuno-modulating and shows the remarkable curative effect on hepatocarcinoma, gastric cancer, lung cacer, breast cancer, at el. So andrographolide is a kind of promising medicine in preventing or treating all kinds of cancers. Some studys showed andrographolide takes an remarkable anti-hepatoma activity. But the curative effect is affect by the lack of hepatic targeting effect. On the other hand, andrographolide is unstability and be apt to be influenced by some environmental factors such as temperature, pH value, at el. Therefore it will play a important role in the emergency treatment to develop a medicine delivery systems to enhance andrographolide hepatic targeting effect and maintain its stability.Niosome is a good kind of drug carrier, nonionic surfactants in hydration medium could be self-assembled into the mini-bilayer vehicles with single cell or multicell. It has the bilayer membrane which is similar to biological membrane, thus it has high affinity with cell membrane and can enhance medicine across membrane transport. Niosome as the medicine release system enfold medicine, on one hand it can increase medicine stability and make medicine release slowly, on the other hand it can take passive targeting effect by controlling its particle size, and then change medicine distribution in vivo. Niosome which is phagocytized chiefly in reticulo-endothelial system in vivo can increase the targeting ability of medicine in liver, spleen, lung and bone marrow and can reach the aim of improving effect and decreasing toxicity.Thus it is the good carrier of targeting drug delivery system.For the drawback of andrographolide inapparent hepatic targeting effect, we construct the administration system of andrographolide niosome. After being encapsulated in the small size vesicles, andrographolide can be targeted passively to the liver, at the same time, the vesicles can make it release slowly and increase its bioavailability.In this paper we do some work on andrographolide niosome, Including:to determine the physics and chemistry character of andrographolide, to optimize preparatian procedure of andrographolide niosome, to study quality standard of andrographolide niosome, to study the tissue distribution characteristics of andrographolide niosome, to determine anti-hepatoma activity of andrographolide niosome in vitro and so on. The whole paper contains the following parts:To study the physics and chemistry character of andrographolide to get ready for preparatian of andrographolide niosome. The partition coefficient of andrographolide in oil phase and aqueous phase is1.42, the order of andrographolide solubility in several organic solvents:Methanol (13.54mg· mL-1)> propylene glycol (9.84mg· mL-1)>absolute alcohol (8.02mg· mL-1)>n-octanol (1.36mg·mL-1)>chloroform (0.36mg·-1), the solubility of andrographolide in the different pH-values phosphate buffer is in the range from20μg·-1 to70μg·mL-1, the content of andrographolide at different pH values(1.8-9.4) at25℃in96h had a less reduction expect pH9.4, the content of andrographolide at different pH values(1.8-9.4) at80℃in24h had a apparent reduction, with a rise of temperature the amount of andrographolide in20%propylene glycol-normal saline solution decrease a little. The above results show that andrographolide is lipophilic, soluble in methanol, absolute alcohol and propylene glycol, hardly in water, stable at25℃and instable at80℃, more stable in20%propylene glycol-normal saline solution. The study of preparatian procedure of drographolide noisome, mainly including, the optimization of prescription and preparation conditions of andrographolide niosome. Using entrapment efficiency, medicine loading rate or the average diameter as evaluation indexes, through a single factor experiment and orthogonal test, the optimized preparation conditions are as following:the film dispersion method was used, span6050mg, cholesterol7.35mg, andrographolide5mg,20%propylene glycol-normal saline solution10mL, hydration rotational Speed125r·min1, hydration time50min, hydration temperature45℃. and then andrographolide niosome is coped with ultrasonic wave under such conditions as ultrasonic power100W,10times,5seconds each time. The andrographolide niosome which is made under the optimized preparation conditions is with the high entrapment efficiency (72.36%), the high medicine loading (5.90%) and the suitable diameter, and comes up to the requirement of hepatic targeting effect. Preparatian procedure of andrographolide niosome is stable, reasonable and feasible.The quality evaluation of andrographolide niosome in some ways. It can been seen by the results, the niosome was intact spherical, uniform and good dispersion, the mean particle diameter is206nm, entrapment efficiency, medicine loading rate and pH value are72.36%,5.90%and8.47respectively, it is stable at4℃, the release kinetics in vitro of andrographolide niosome meets Higuchi kinetic equation, about65%of andrographolide release in24h. Andrographolide niosome is in accordance with quality request and hepatic targeting request. To identify andrographolide niosome by Infrared spectrum and DSC. The IR pictures show, there is some difference between andrographolide niosome and raw materials, two obvious new absorption peak appears in the Fingerprint area of andrographolide niosome, the absorption peak of andrographolide1646.94cm-1 is disappear. The DSC pictures show, there are the double endothermic peaks for andrographolide niosome, the heat-absorbing capacity per gram fall markedly. These indicate the niosome has formed and andrographolide is enclosed into the bilayer well.Research on the tissue distribution characteristics of andrographolide niosome injected via mice caudal vein. To analyze the medicine concentration and medicine concentration-time curve in each tissue between andrographolide niosome group and andrographolide solution group. To fit the best compartment model and pharmacokinetic parameters AUC(0→00), Cmax and MRT(0→∞) of each tissue by DAS2.1.1pharmacokinetic program, to calculate the targeting parameters Te and Ce. The results are shown, each tissue matches up to two-compartment open mode(C=Ae-αt+Beβt, hepatic targeting efficiency Te of andrographolide niosome and andrographolide solution is3.66and0.62respectively, comparing andrographolide niosome group and andrographolide solution group, the proportionality of peak Concentration in liver Ce is2.45, MRT(0-∞) increase obviously. A conclusion is as following, niosome can improve andrographolide hepatic targeting effect markedly and make medicine release slowly.An experimental study of anti-HepG2cell of andrographolide niosome in vitro. To determine the effect of andrographolide niosome on the survival rate of HepG2cell by MTT test and on the expression of Bcl-2mRNA and Bax mRNA by RT-PCR. Results show that andrographolide niosome can lower the survival rate of HepG2cell, increase Bax mRNA expression and decrease Bcl-2mRNA expression. Results reveal that andrographolide niosome can inhibit HepG2cell obviously.In summary, following the optimized preparation conditions we develop andrographolide niosome successfully, the preparation process is steady, feasible and with good reproducibility, the quality of andrographolide niosome is stable and controlled, andrographolide niosome shows the obvious effect of hepatic targeting and slow-releasing medicine. So it is successful to achieved the object of the present study, at the same time it makes a good foundation for exploitation of correlative new medicine.In this paper, in the course of andrographolide niosome preparation, some innovation and explore are as follow:For the drawback of inapparent hepatic targeting effect and instability of andrographolide, It is the first time to develop andrographolide niosome. andrographolide niosome with the high entrapment efficiency (72.36%) and the high medicine loading (5.90%) shows the obvious effect of hepatic targeting and slow-releasing medicine, it is the new train of thought to develop new drug of treating liver cancer.To choose20%propylene glycol-normal saline solution as hydration medium. First,20%propylene glycol-normal saline solution is low toxicity. Secondly, andrographolide niosome can form in the20%propylene glycol-normal saline solution. Thirdly, andrographolide can dissolve a little in20%propylene glycol-normal saline solution, the part of andrographolide which is not encapsulated can be embeded in the bi-layer in molecular form continuously, so it is benefit to increase the entrapment efficiency.
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