| Liposome as known as lipid ball is composed by insoluble phospholipids and other additives suchas cholesterol, and it is a micro-vesicle that is caused by drug encapsulated in the class of lipidphospholipids. Liposome has phospholipids bilayer similar to the biofilm , which is particularly applicableto the targeted therapyit of the insoluble anticancer drugs,because of the solubioizing effect, which iscarreried out by containing the insoluble drug in the lipid molecular sandwich, and the increased drugtherapeutic index caused by the vivo distribution of the contained drugs and the reduced toxicity . As a newdrug carrier, liposome not only can improve the drugs safety, effectiveness, stability and patientcompliance ,but also can reduce adverse drug reactions. Therefore, liposome has great potential as a drugdelivery system.Andrographolide is a diterpene lactones from Andrographis paniculata (Burm.f ) Nees, which has theeffect of antibacterial fever,cough and asthma ,and it is used for the treatment of airway inflammation andbacterial dysentery in the clinical. Modern research found that andrograpHolide and its derivatives haveanti-tumor and immunomdulatory role. AndrograpHolide derivatives ATC-Ⅱwhich has synthesized by ourresearch group , has obviously anti-tumor effect, but its efficacy of play is bad because of low watersolubility, poor oral absorption and low bioavailability.This paper used Andrographolide derivatives ATC-Ⅱas a model drug and investigated the efficiencyof some factors ,such as preparation methods ,prescription formulate and preparation process, to theencapsulation efficiency of ATC -Ⅱ-loaded liposomes. In addition ,we made a systematic study to itspharmacy property , pharmacokinetics of rats after intravenous injection and tissue distribution afterintravenous injection in mice.ATC-Ⅱ-loaded liposomes were prepared by film dispersion method and the prescription andpreparation processthe were determined after the single factor method.The result showed that dosage ofdrug, dosage of cholesterol,and hydration volume were the influence factors.Average particle size,encapsulation efficiency and drug loadings were used as the evaluation parameters, and response surfacemethod was used to optimize formulation and process. The content determination was conducted by HPLCand drug loadings was conducted by ultrafiltration. According to the optimization conditions, the average particle size, encapsulation efficiency and drug loading were (146.3±2.47)nm, (88.54±1.12)% ,(3.16±0.06)% respectively.The research of pharmacy property showed that ATC -Ⅱ-loaded liposomes has good stability andthe research of release in vitro revealed that ATC -Ⅱ-loaded liposomes have sustained releasecharacteristics .Riger-Peppas is the optimal equation in vitro release, which descripes that drug releasethrough the lipid layer diffusion.As a result, ATC -Ⅱloaded in liposomes has sustained releasecharacteristics .The pharmacokinetic characteristics of a single dose intravenous injection of ATC -Ⅱ-loadedliposomes compared with that of ATC -Ⅱsolution in rats were investigated , and the datas were calculatedby means of 3p97. According to compartment-model fitting results, ATC -Ⅱ-loaded liposomes and ATC -Ⅱsolution were both fitted with two compartment-model.T1/2βof ATC -Ⅱ-loaded liposomes and solutionwere 7.07h and 5.14h pectively, and the clearance rate were 0.0091mg/kg/h/(μg/mL) and 0.0163mg/kg/h/(μg/mL). As the results calculated according to statistical moment theory：AUC of ATC -Ⅱ-loaded liposomes and solution were 102.87（μg/mL）*h and 52.84（μg/mL）*h，and MRT were 7.44hand 6.03h. The result showed that ,compared with the solution, ATC -Ⅱ-loaded liposomes can prolongthe circulation time of drugs.The study of tissue distribution in mice of ATC -Ⅱ-loaded-liposomes showed that the distributionin the plasma, liver and spleen were increased,compared with solution ,and AUC were 1.48,2.13,1.66times .There is no significant difference in lung and kidney while the AUC was 0.72 times in heart,so ATC-Ⅱ-loaded-liposomes reduced the distribution in the heart and reduced the cardigan toxicity.Therefore, theliposomes have the live and spleen targeting. |
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