Research Of Plumbagin Liposomes An A Drug Delivery System

Plumbago zeylanica L.is widespread in Southeast Asia and South and Southwest China.In recent years,researchers have been paying much attention on plumbagin,a compound extracted from this plant.Studies showed that plumbagin had a wide range of pharmacological activities,such as anti-cancer, radiation protection,anti-bacteria,pesticide,and so on.However,due to its poor water solubility,toxicity,low melting point and sublimation,this compound has been lagged in development and utilization.In our study,we sought to make plumbagin into liposomes,which wrapped the fat-soluble plumbagin to increase its concentration in water and reduce the percentage of organic solvents in products on one hand,and were organ-targeted and lower in toxicity on the other hand.This paper fell into three parts.In partâ… ,plumbagin was isolated from the root of P.zeytanica L.by silica gel column chromatography and confirmed by MS,IR,¹H-NMR and ¹³C-NMR. Plumbagin is fatsoluble drug,and PEG400 do better result on solubilization. Next,with the MTT method,growth inhibitory effects of plumbagin and its modified products to human tumour cells were studied,the results showing that plumbagin possessed strong and wide-range anti-cancer activity while its modified products had a much narrower range of anti-cancer activity though they exhibited a greater inhibitory action on some types of cancer cells.Then, we developed a HPLC-UV method for determining the content of plumbagin in samples,through which plumbagin could be separated from other matters and detected easily,quickly and accurately.Partâ…¡was about plumbagin liposome's preparation techniques.In this part, methods were developed to determine the structure,particle size distribution, content,encapsulation efficiency,leakage rate and drug loading of production, on the basis of which the afterward relevant experiments could be assessed.By use of single factor screening,we found that the film-ultrasonic method was suitable for preparing liposomes in laboratory.Using Plackett-Burman design, we determined some key factors as follows:30 mL pure water(pH 6.5)was the medium,after 3 hours of hydration,the solution was handled with an ultrasonic apparatus(400W)for 20 minutes.Through using response surface methodology, we gained the optimal liposome composition:plumbagin 20mg,phospholipids 700mg,cholesterol 500mg and F-68 100mg.Since the inclusion of liquid liposomes was apt to aggregate and precipitate during storage,with freeze-drying technology we transformed them into cryodesiccated agents, which met the requirement in characteristics,color,solubility and water content. In order to estimate the stability of the agents,we conducted some related tests——light and heat,whose results revealed that the agents were sensitive to light and were stable at 4℃.In the final part,we observed the acute toxicity effects of plumbagin solution, plumbagin liposome and plumbagin-Cu on mice via i.v.,results indicating that the latter two compounds were obviously lower than the former one in toxicity (p＜0.01),and that sex of mice had no significantly different influences on the action of all the drugs(p＞0.05).Compared with those treated with plumbagin solution,mice treated with plumbagin liposome had higher drug content and AUC in their plasma and tissues.Besides,high level of r_e,R_Kcand C_e were found in liver and spleen of mice which treated with plumbagin liposome, results demonstrated that plumbagin liposomes had liver and spleen targeting property to some extent.